The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

PubMed Central

den Besten, Gijs; van Eunen, Karen; Groen, Albert K.; Venema, Koen; Reijngoud, Dirk-Jan; Bakker, Barbara M.

2013-01-01

Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism. PMID:23821742

Dynamics of vegetation autumn phenology and its response to multiple environmental factors from 1982 to 2012 on Qinghai-Tibetan Plateau in China.

PubMed

Li, Peng; Peng, Changhui; Wang, Meng; Luo, Yunpeng; Li, Mingxu; Zhang, Kerou; Zhang, Dingling; Zhu, Qiuan

2018-05-11

Autumn phenological shifts induced by environmental change have resulted in substantial impacts on ecosystem processes. However, autumn phenology and its multiple related controlling factors have not been well studied. In this study, the spatiotemporal patterns of the end date of the vegetation growing season (EGS) and their multiple controls (climate change, summer vegetation growth and human activities) over the Qinghai-Tibetan Plateau (QTP) were investigated using the satellite-derived normalized difference vegetation index (NDVI) based on GIMMS3g datasets during 1982-2012. The results showed that there was no significant temporal trend in the EGS during the period of 1982-2012. Spatially, there was a notable advancing trend in the southwest region and a delayed trend in the other regions of the QTP during 1982-2000, and this spatial trend was reversed during 2001-2012. We found average temperature, precipitation and sunshine duration of autumn exerted positive effects on EGS on the QTP, while average temperature and sunshine duration of summer exerted negative effects. Our results indicated that vegetation growth in summer tends to induce an earlier EGS in alpine vegetation, whereas summer vegetation degradation could delay the EGS on the QTP. In contrast, moderate grazing delays vegetation browning in autumn, while overgrazing leads to advancement of grass senescence. This study improves our understanding of how multiple environmental variables jointly affect autumn phenology and highlights the importance of biotic controls for autumn phenology on the QTP. Copyright © 2017 Elsevier B.V. All rights reserved.

Shifting from the single- to the multitarget paradigm in drug discovery

PubMed Central

Medina-Franco, José L.; Giulianotti, Marc A.; Welmaker, Gregory S.; Houghten, Richard A.

2013-01-01

Increasing evidence that several drug compounds exert their effects through interactions with multiple targets is boosting the development of research fields that challenge the data reductionism approach. In this article, we review and discuss the concepts of drug repurposing, polypharmacology, chemogenomics, phenotypic screening and highthroughput in vivo testing of mixture-based libraries in an integrated manner. These research fields offer alternatives to the current paradigm of drug discovery, from a one target–one drug model to a multiple-target approach. Furthermore, the goals of lead identification are being expanded accordingly to identify not only ‘key’ compounds that fit with a single-target ‘lock’, but also ‘master key’ compounds that favorably interact with multiple targets (i.e. operate a set of desired locks to gain access to the expected clinical effects). PMID:23340113

Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro.

PubMed

Al-Dwairi, Ahmed; Alqudah, Tamara E; Al-Shboul, Othman; Alqudah, Mohammad; Mustafa, Ayman G; Alfaqih, Mahmoud A

2018-01-01

Intestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms. The aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS). Freshly isolated CSMCs from male BALB/c mice were cultured in DMEM and treated with vehicle, LPS (1 μg/mL), LPS+exendin-4 (50 nM), or LPS+exendin-4 (100 nM) for 24 h. Expression of inflammatory cytokines was then evaluated by antibody array membrane. CSMCs showed basal expression of several cytokines which was enhanced with the induction of inflammation by LPS. However, exendin-4 (50 and 100 nM) significantly ( p <0.05) reduced the expression of multiple cytokines including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), T cell activation gene-3 (TCA-3), stromal cell-derived factor-1 (SDF-1), and macrophage colony stimulating factor (M-CSF). To confirm these results, expression of these cytokines was further assessed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction and similar results were also observed. Moreover, secretion of TNF-α and IL1-α into the conditioned media was significantly downregulated by exendin-4 when compared to LPS-treated cells. Furthermore, LPS increased NF-κB phosphorylation, while exendin-4 significantly reduced levels of NF-κB phosphorylation. These data indicate that GLP-1 analogs can exert significant anti-inflammatory effects on CSMCs and can potentially be used as an adjunct treatment for inflammatory bowel conditions.

Public health benefits of strategies to reduce greenhouse-gas emissions: health implications of short-lived greenhouse pollutants.

PubMed

Smith, Kirk R; Jerrett, Michael; Anderson, H Ross; Burnett, Richard T; Stone, Vicki; Derwent, Richard; Atkinson, Richard W; Cohen, Aaron; Shonkoff, Seth B; Krewski, Daniel; Pope, C Arden; Thun, Michael J; Thurston, George

2009-12-19

In this report we review the health effects of three short-lived greenhouse pollutants-black carbon, ozone, and sulphates. We undertook new meta-analyses of existing time-series studies and an analysis of a cohort of 352,000 people in 66 US cities during 18 years of follow-up. This cohort study provides estimates of mortality effects from long-term exposure to elemental carbon, an indicator of black carbon mass, and evidence that ozone exerts an independent risk of mortality. Associations among these pollutants make drawing conclusions about their individual health effects difficult at present, but sulphate seems to have the most robust effects in multiple-pollutant models. Generally, the toxicology of the pure compounds and their epidemiology diverge because atmospheric black carbon, ozone, and sulphate are associated and could interact with related toxic species. Although sulphate is a cooling agent, black carbon and ozone could together exert nearly half as much global warming as carbon dioxide. The complexity of these health and climate effects needs to be recognised in mitigation policies. Copyright 2009 Elsevier Ltd. All rights reserved.

Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin.

PubMed

Zhao, Sufen; Ye, Gang; Fu, Guodong; Cheng, Jian-Xin; Yang, Burton B; Peng, Chun

2011-05-01

Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin.

Public health benefits of strategies to reduce greenhouse-gas emissions: health implications of short-lived greenhouse pollutants

PubMed Central

Smith, Kirk R.; Jerrett, Michael; Anderson, H Ross; Burnett, Richard T.; Stone, Vicki; Derwent, Richard; Atkinson, Richard W.; Cohen, Aaron; Shonkoff, Seth B.; Krewski, Daniel; Pope, C. Arden; Thun, Michael J.; Thurston, George

2014-01-01

In this report we review the health effects of three short-lived greenhouse pollutants—black carbon, ozone, and sulphates. We undertook new meta-analyses of existing time-series studies and an analysis of a cohort of 352 000 people in 66 US cities during 18 years of follow-up. This cohort study provides estimates of mortality effects from long-term exposure to elemental carbon, an indicator of black carbon mass, and evidence that ozone exerts an independent risk of mortality. Associations among these pollutants make drawing conclusions about their individual health effects difficult at present, but sulphate seems to have the most robust effects in multiple-pollutant models. Generally, the toxicology of the pure compounds and their epidemiology diverge because atmospheric black carbon, ozone, and sulphate are associated and could interact with related toxic species. Although sulphate is a cooling agent, black carbon and ozone could together exert nearly half as much global warming as carbon dioxide. The complexity of these health and climate effects needs to be recognised in mitigation policies. PMID:19942276

Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades

PubMed Central

Lee, Hanwool; Baek, Seung Ho; Lee, Jong Hyun; Kim, Chulwon; Ko, Jeong-Hyeon; Lee, Seok-Geun; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Yang, Woong Mo; Um, Jae-Young; Sethi, Gautam; Ahn, Kwang Seok

2017-01-01

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells. PMID:28534824

Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades.

PubMed

Lee, Hanwool; Baek, Seung Ho; Lee, Jong Hyun; Kim, Chulwon; Ko, Jeong-Hyeon; Lee, Seok-Geun; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Yang, Woong Mo; Um, Jae-Young; Sethi, Gautam; Ahn, Kwang Seok

2017-05-19

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.

Controlling subcellular delivery to optimize therapeutic effect

PubMed Central

Mossalam, Mohanad; Dixon, Andrew S; Lim, Carol S

2010-01-01

This article focuses on drug targeting to specific cellular organelles for therapeutic purposes. Drugs can be delivered to all major organelles of the cell (cytosol, endosome/lysosome, nucleus, nucleolus, mitochondria, endoplasmic reticulum, Golgi apparatus, peroxisomes and proteasomes) where they exert specific effects in those particular subcellular compartments. Delivery can be achieved by chemical (e.g., polymeric) or biological (e.g., signal sequences) means. Unidirectional targeting to individual organelles has proven to be immensely successful for drug therapy. Newer technologies that accommodate multiple signals (e.g., protein switch and virus-like delivery systems) mimic nature and allow for a more sophisticated approach to drug delivery. Harnessing different methods of targeting multiple organelles in a cell will lead to better drug delivery and improvements in disease therapy. PMID:21113240

Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

PubMed

Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, R J

2011-08-01

Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32-5.6 mg/kg] and cocaine [0.32-10 mg/kg]) and two sedatives (chlordiazepoxide [1.78-32 mg/kg] and pentobarbital [1.0-17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32-3.2 mg/kg] and pentobarbital [1.8-10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. (c) 2011 APA, all rights reserved.

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

PubMed Central

Oláh, Attila; Tóth, Balázs I.; Borbíró, István; Sugawara, Koji; Szöllõsi, Attila G.; Czifra, Gabriella; Pál, Balázs; Ambrus, Lídia; Kloepper, Jennifer; Camera, Emanuela; Ludovici, Matteo; Picardo, Mauro; Voets, Thomas; Zouboulis, Christos C.; Paus, Ralf; Bíró, Tamás

2014-01-01

The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris. PMID:25061872

Translations on Eastern Europe Political, Sociological, and Military Affairs No. 1373.

DTIC Science & Technology

1977-04-01

the fact that at most of the meetings, party and non- party members made statements even more critical and self -critical than the reports submitted...same time, by inertia, the old concepts and attitudes toward productive labor, particularly on the part of parents , continue to exert a serious...sectors as well. Achieving a multiplication effect is not a self -seeking aim. Above all, in order to apply a given scientific or technical

High self-perceived exercise exertion before bedtime is associated with greater objectively assessed sleep efficiency.

PubMed

Brand, Serge; Kalak, Nadeem; Gerber, Markus; Kirov, Roumen; Pühse, Uwe; Holsboer-Trachsler, Edith

2014-09-01

To assess the association between self-perceived exercise exertion before bedtime and objectively measured sleep. Fifty-two regularly exercising young adults (mean age, 19.70 years; 54% females) underwent sleep electroencephalographic recordings 1.5 h after completing moderate to vigorous exercise in the evening. Before sleeping, participants answered questions regarding degree of exertion of the exercise undertaken. Greater self-perceived exertion before bedtime was associated with higher objectively assessed sleep efficiency (r = 0.69, P <0.001); self-perceived exertion explained 48% of the variance in sleep efficiency (R2 = 0.48). Moreover, high self-perceived exercise exertion was associated with more deep sleep, shortened sleep onset time, fewer awakenings after sleep onset, and shorter wake duration after sleep onset. Multiple linear regression analysis showed that objective sleep efficiency was predicted by increased exercise exertion, shortened sleep onset time, increased deep sleep, and decreased light sleep. Against expectations and general recommendations for sleep hygiene, high self-perceived exercise exertion before bedtime was associated with better sleep patterns in a sample of healthy young adults. Further studies should also focus on elderly adults and adults suffering from insomnia. Copyright © 2014 Elsevier B.V. All rights reserved.

Biologic effects of interferons.

PubMed

Gresser, I

1990-12-01

If one were to review articles on IFN published between 1957 and 1967 it would become apparent that virtually none of the tenets held then are still valid today. Whereas IFN was long considered to be a specific antiviral substance without any effect on normal cellular metabolism, we accept today that it affects normal cell division and many specialized cellular functions. In this respect it is not unique; IFN is a prototype of a family of similar substances now called cytokines that all appear to function as regulatory molecules. It was held that the production of IFN constituted a specific response to a viral infection. Today we believe that IFN is an integral part of a cytokine network and that they and other cytokines may be produced constitutively at low levels. These substances exert multiple effects on virtually all cells. They play an important role in host defense against viral and parasitic infections, and in the resistance to experimental tumors. IFN can be shown to exert effects on the immune system and on lymphocyte circulation. Lastly, because of the multiplicity of their biologic effects, they may even contribute to the pathogenesis of certain diseases. Thus, when large amounts of IFN are administered or induced in newborn mice they can cause liver, kidney, and pulmonary disease. The field of IFN and cytokine research continues to expand and there is an increasing number of therapeutic applications. Twenty years from now, scientists and clinicians may be surprised that we understood so little of how IFN act and how inadequately we used them to treat disease.

GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters.

PubMed

Ramesh, Sunita A; Tyerman, Stephen D; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A; Ryan, Peter R; Gilliham, Matthew; Gillham, Matthew

2015-07-29

The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms.

GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters

PubMed Central

Ramesh, Sunita A.; Tyerman, Stephen D.; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A.; Ryan, Peter R.; Gillham, Matthew

2015-01-01

The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms. PMID:26219411

Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

PubMed Central

Zhang, Li; Wang, Handong

2015-01-01

Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma (PPARγ). Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX. PMID:26184238

Examining Effects of Physical Exertion on the Dynamic Visual Acuity Test in Collegiate Athletes.

PubMed

Patterson, Jessie N; Murphy, Anna M; Honaker, Julie A

2017-01-01

Acute symptoms of dizziness and/or imbalance commonly experienced in athletes postconcussion are speculated to arise from dysfunction at multiple levels (i.e., inner ear or central vestibular system) to appropriately integrate afferent sensory information. Disruption along any pathway of the balance system can result in symptoms of dizziness, decreased postural control function (vestibulospinal reflex), and reduced vestibulo-ocular reflex function. This may also lead to decreased gaze stability with movements of the head and may account for symptoms of blurred vision or diplopia reported in almost half of athletes sustaining a concussion. Current concussion position statements include measures of postural control to examine changes to the balance system postconcussion. The Balance Error Scoring System (BESS) is a commonly used low-cost postural control measure for concussion assessment. Although this is a widely used measure for documenting balance function on both immediate (sideline) and recovery monitoring, the BESS has been shown to be affected by physical exertion. Therefore, the BESS may not be the most efficient means of examining functional changes to the balance system immediately after head injury. Dynamic Visual Acuity Test (DVAT) has been found to effectively evaluate and monitor changes to the gaze stability system postinjury. Thus, DVAT may be an additional measure in the concussion assessment battery, as well as an alternative for more immediate sideline assessment to help make objective return-to-play decisions. The aim of the study was to determine the effects of physical exertion on a clinical vestibular assessment, the DVAT, in collegiate athletes, as a first step in defining the role of this measure in the concussion assessment battery. Cross-sectional, repeated-measures design. Twenty-eight healthy collegiate athletes (20 males, 8 females; age = 20.25 ± 1.46 yr, range = 18-25 yr) volunteered to participate in the study. Participants were randomly assigned to complete a 20-min protocol of physical exertion or rest. DVAT was completed pre-exertion or rest (pre-DVAT), immediately following the 20-min protocol (post-DVAT I), and again 10 min after the completion of the 20-min protocol (post-DVAT II). Ratings of perceived exertion (RPE) and heart rate (HR) were monitored throughout testing. Repeated-measures analysis of the variance were used to examine the effects of exertion on DVAT. Additionally, intraclass correlation coefficients were used to examine test reliability. No significant main effect was observed for right and left DVAT logarithm of the minimal angle of resolution loss between groups or across time points (p > 0.05). A significant main effect was observed for RPE and HR for groups and time points (p < 0.001), indicating adequate physical exertion and rest. Fair to good reliability (intraclass correlation coefficient values between 0.4 and 0.74) was observed for both rightward and leftward movements of the head across the three time points. Findings from this study suggest that DVAT is not affected by physical exertion and may provide a more immediate assessment of the balance system that may be of use for the sideline concussion assessment. Future studies will be performed to examine additional factors (e.g., background noise, complex visual backgrounds) that may affect DVAT performance in the sideline environment. American Academy of Audiology

Pharmacotherapeutics directed at deficiencies associated with cocaine dependence: Focus on dopamine, norepinephrine and glutamate

PubMed Central

Haile, Colin N.; Mahoney, James J.; Newton, Thomas F.; De La Garza, Richard

2012-01-01

Much effort has been devoted to research focused on pharmacotherapies for cocaine dependence yet there are no FDA-approved medications for this brain disease. Preclinical models have been essential to defining the central and peripheral effects produced by cocaine. Recent evidence suggests that cocaine exerts its reinforcing effects by acting on multiple neurotransmitter systems within mesocorticolimibic circuitry. Imaging studies in cocaine-dependent individuals have identified deficiencies in dopaminergic signaling primarily localized to corticolimbic areas. In addition to dysregulated striatal dopamine, norepinephrine and glutamate are also altered in cocaine dependence. In this review, we present these brain abnormalities as therapeutic targets for the treatment of cocaine dependence. We then survey promising medications that exert their therapeutic effects by presumably ameliorating these brain deficiencies. Correcting neurochemical deficits in cocaine-dependent individuals improves memory and impulse control, and reduces drug craving that may decrease cocaine use. We hypothesize that using medications aimed at reversing known neurochemical imbalances is likely to be more productive than current approaches. This view is also consistent with treatment paradigms used in neuropsychiatry and general medicine. PMID:22327234

Sasa health exerts a protective effect on Her2/NeuN mammary tumorigenesis.

PubMed

Ren, Mingqiang; Reilly, R Todd; Sacchi, Nicoletta

2004-01-01

Bamboo grass leaves of different Sasa species have been widely used in food and medicine in Eastern Asia for hundreds of years. Of special interest are Kumazasa (Sasa senanensis rehder) leaves used to prepare an alkaline extract known as Sasa Health. This extract was reported to inhibit both the development and growth of mammary tumors in a mammary tumor strain of virgin SHN mice (1). We found that Sasa Health exerts a significant protective effect on spontaneous mammary tumorigenesis in another mouse model of human breast cancer, the transgenic FVB-Her2/NeuN mouse model. Two cohorts of Her2/NeuN female mice of different age (eleven-week-old and twenty-four-week-old) chronically treated with Sasa Health in drinking water showed both a delay in the development of tumors and reduced tumor multiplicity. Sasa Health also induced inhibition of mammary duct branching and side bud development in association with reduced angiogenesis. Altogether these findings indicate that Sasa Health contains phytochemicals that can effectively retard spontaneous mammary tumorigenesis.

Therapeutic role of rifampicin in Alzheimer's disease.

PubMed

Yulug, Burak; Hanoglu, Lütfü; Ozansoy, Mehmet; Isık, Dogan; Kilic, Ulkan; Kilic, Ertugrul; Schabitz, Wolf Rüdiger

2018-03-01

Rifampicin exerts significant brain protective functions in multiple experimental models. Here we summarize the underlying mechanisms of the neuroprotective and pro-cognitive effects of rifampicin that are mediated by its anti-inflammatory, anti-tau, anti-amyloid, and cholinergic effects. Beyond suggesting that rifampicin shows strong brain protective effects in preclinical models of Alzheimer's disease, we also provide substantial clinical evidence for the neuroprotective and pro-cognitive effects of rifampicin. Future neuroimaging studies combined with clinical assessment scores are the following steps to be taken in this field of research. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

Selective targeting of KRAS-Mutant cells by miR-126 through repression of multiple genes essential for the survival of KRAS-Mutant cells

PubMed Central

Hara, Toshifumi; Jones, Matthew F.; Subramanian, Murugan; Li, Xiao Ling; Ou, Oliver; Zhu, Yuelin; Yang, Yuan; Wakefield, Lalage M.; Hussain, S. Perwez; Gaedcke, Jochen; Ried, Thomas; Luo, Ji; Caplen, Natasha J.; Lal, Ashish

2014-01-01

MicroRNAs (miRNAs) regulate the expression of hundreds of genes. However, identifying the critical targets within a miRNA-regulated gene network is challenging. One approach is to identify miRNAs that exert a context-dependent effect, followed by expression profiling to determine how specific targets contribute to this selective effect. In this study, we performed miRNA mimic screens in isogenic KRAS-Wild-type (WT) and KRAS-Mutant colorectal cancer (CRC) cell lines to identify miRNAs selectively targeting KRAS-Mutant cells. One of the miRNAs we identified as a selective inhibitor of the survival of multiple KRAS-Mutant CRC lines was miR-126. In KRAS-Mutant cells, miR-126 over-expression increased the G1 compartment, inhibited clonogenicity and tumorigenicity, while exerting no effect on KRAS-WT cells. Unexpectedly, the miR-126-regulated transcriptome of KRAS-WT and KRAS-Mutant cells showed no significant differences. However, by analyzing the overlap between miR-126 targets with the synthetic lethal genes identified by RNAi in KRAS-Mutant cells, we identified and validated a subset of miR-126-regulated genes selectively required for the survival and clonogenicity of KRAS-Mutant cells. Our strategy therefore identified critical target genes within the miR-126-regulated gene network. We propose that the selective effect of miR-126 on KRAS-Mutant cells could be utilized for the development of targeted therapy for KRAS mutant tumors. PMID:25245095

In Vitro Effect of Malachite Green on Candida albicans Involves Multiple Pathways and Transcriptional Regulators UPC2 and STP2

PubMed Central

Dhamgaye, Sanjiveeni; Devaux, Frederic; Manoharlal, Raman; Vandeputte, Patrick; Shah, Abdul Haseeb; Singh, Ashutosh; Blugeon, Corinne; Sanglard, Dominique

2012-01-01

In this study, we show that a chemical dye, malachite green (MG), which is commonly used in the fish industry as an antifungal, antiparasitic, and antibacterial agent, could effectively kill Candida albicans and non-C. albicans species. We have demonstrated that Candida cells are susceptible to MG at a very low concentration (MIC that reduces growth by 50% [MIC50], 100 ng ml−1) and that the effect of MG is independent of known antifungal targets, such as ergosterol metabolism and major drug efflux pump proteins. Transcriptional profiling in response to MG treatment of C. albicans cells revealed that of a total of 207 responsive genes, 167 genes involved in oxidative stress, virulence, carbohydrate metabolism, heat shock, amino acid metabolism, etc., were upregulated, while 37 genes involved in iron acquisition, filamentous growth, mitochondrial respiration, etc., were downregulated. We confirmed experimentally that Candida cells exposed to MG resort to a fermentative mode of metabolism, perhaps due to defective respiration. In addition, we showed that MG triggers depletion of intracellular iron pools and enhances reactive oxygen species (ROS) levels. These effects could be reversed by the addition of iron or antioxidants, respectively. We provided evidence that the antifungal effect of MG is exerted through the transcription regulators UPC2 (regulating ergosterol biosynthesis and azole resistance) and STP2 (regulating amino acid permease genes). Taken together, our transcriptome, genetic, and biochemical results allowed us to decipher the multiple mechanisms by which MG exerts its anti-Candida effects, leading to a metabolic shift toward fermentation, increased generation of ROS, labile iron deprivation, and cell necrosis. PMID:22006003

How does the multifaceted plant hormone salicylic acid combat disease in plants and are similar mechanisms utilized in humans?

PubMed

Dempsey, D'Maris Amick; Klessig, Daniel F

2017-03-23

Salicylic acid (SA) is an important plant hormone that regulates many aspects of plant growth and development, as well as resistance to (a)biotic stress. Efforts to identify SA effector proteins have revealed that SA binds to and alters the activity of multiple plant proteins-this represents a shift from the paradigm that hormones mediate their functions via one or a few receptors. SA and its derivatives also have multiple targets in animals; some of these proteins, like their plant counterparts, are associated with pathological processes. Together, these findings suggest that SA exerts its defense-associated effects in both kingdoms via a large number of targets.

Antibiofilm and Anti-Inflammatory Activities of Houttuynia cordata Decoction for Oral Care

PubMed Central

Sekita, Yasuko; Hirao, Kouji; Amoh, Takashi; Hirota, Katsuhiko; Fujii, Hideki; Matsuo, Takashi; Miyake, Yoichiro; Kashiwada, Yoshiki

2017-01-01

Dental biofilms that form in the oral cavity play a critical role in the pathogenesis of several infectious oral diseases, including dental caries, periodontal disease, and oral candidiasis. Houttuynia cordata (HC, Saururaceae) is a widely used traditional medicine, for both internal and external application. A decoction of dried HC leaves (dHC) has long been consumed as a health-promoting herbal tea in Japan. We have recently reported that a water solution of HC poultice ethanol extract (wHCP) exerts antimicrobial and antibiofilm effects against several important oral pathogens. It also exhibits anti-inflammatory effects on human keratinocytes. In our current study, we examined the effects of dHC on infectious oral pathogens and inflammation. Our results demonstrated that dHC exerts moderate antimicrobial effects against methicillin-resistant Staphylococcus aureus (MRSA) and other oral microorganisms. dHC also exhibited antibiofilm effects against MRSA, Fusobacterium nucleatum (involved in dental plaque formation), and Candida albicans and inhibitory effects on interleukin-8, CCL20, IP-10, and GROα productions by human oral keratinocytes stimulated by Porphyromonas gingivalis lipopolysaccharide (a cause of periodontal disease), without cytotoxic effects. This suggests that dHC exhibits multiple activities in microorganisms and host cells. dHC can be easily prepared and may be effective in preventing infectious oral diseases. PMID:29234378

Antibiofilm and Anti-Inflammatory Activities of Houttuynia cordata Decoction for Oral Care.

PubMed

Sekita, Yasuko; Murakami, Keiji; Yumoto, Hiromichi; Hirao, Kouji; Amoh, Takashi; Fujiwara, Natsumi; Hirota, Katsuhiko; Fujii, Hideki; Matsuo, Takashi; Miyake, Yoichiro; Kashiwada, Yoshiki

2017-01-01

Dental biofilms that form in the oral cavity play a critical role in the pathogenesis of several infectious oral diseases, including dental caries, periodontal disease, and oral candidiasis. Houttuynia cordata (HC, Saururaceae) is a widely used traditional medicine, for both internal and external application. A decoction of dried HC leaves (dHC) has long been consumed as a health-promoting herbal tea in Japan. We have recently reported that a water solution of HC poultice ethanol extract (wHCP) exerts antimicrobial and antibiofilm effects against several important oral pathogens. It also exhibits anti-inflammatory effects on human keratinocytes. In our current study, we examined the effects of dHC on infectious oral pathogens and inflammation. Our results demonstrated that dHC exerts moderate antimicrobial effects against methicillin-resistant Staphylococcus aureus (MRSA) and other oral microorganisms. dHC also exhibited antibiofilm effects against MRSA, Fusobacterium nucleatum (involved in dental plaque formation), and Candida albicans and inhibitory effects on interleukin-8, CCL20, IP-10, and GRO α productions by human oral keratinocytes stimulated by Porphyromonas gingivalis lipopolysaccharide (a cause of periodontal disease), without cytotoxic effects. This suggests that dHC exhibits multiple activities in microorganisms and host cells. dHC can be easily prepared and may be effective in preventing infectious oral diseases.

Genistein, a dietary soy isoflavone, exerts antidepressant-like effects in mice: Involvement of serotonergic system.

PubMed

Hu, Pei; Ma, Li; Wang, Yan-Gui; Ye, Feng; Wang, Chuang; Zhou, Wen-Hua; Zhao, Xin

2017-09-01

Genistein, a principal isoflavone property of soybeans, possesses multiple pharmacological activities such as neuroprotection. Recently, it was reported that genistein exerted antidepressant-like effects in animal models, but the mechanism of action remains ambiguous. The purpose of this study was to investigate the antidepressant-like effect of genistein in mice and explore the underlying mechanism(s), using two mouse models of depression, i.e. forced swim test (FST) and tail suspension test (TST). Chronic, but not acute (single dose), genistein treatment (5, 15 or 45 mg/kg, p.o., once per day for three weeks) exerted dose-dependently antidepressant-like effect in mice, concomitant with escalated levels of brain monoamines and suppressed monoamine oxidase (MAO) activity. Chemical depletion of brain serotonin by PCPA abrogated the antidepressant-like action of genistein, but it was not the case for ablation of NA by DSP-4. Moreover, the anti-depression by genistein was preferentially counteracted by co-administration of 5-HT 1A receptor antagonist WAY-100635, suggesting a pivotal role for 5-HT system coupled with 5-HT 1A receptors in mediating such genistein anti-depression. This point was further validated by the fact that genistein action was potentiated by co-treatment with 8-OH-DPAT, a selective 5-HT 1A receptor agonist. Collectively, these findings confirm that chronic genistein administration to mice engenders antidepressant-like efficacy evidenced by lessened behavioral despair. Serotonergic system that preferentially couples with 5-HT 1A receptors may be critically responsible for the present genistein anti-depression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lactate and pH evaluation in exhausted humans with prolonged TASER X26 exposure or continued exertion.

PubMed

Ho, Jeffrey D; Dawes, Donald M; Cole, Jon B; Hottinger, Julie C; Overton, Kenneth G; Miner, James R

2009-09-10

Safety concerns about TASER Conducted Electrical Weapon (CEW) use and media reports of deaths after exposure have been expressed. CEWs are sometimes used on exhausted subjects to end resistance. The alternative is often a continued struggle. It is unclear if CEW use is metabolically different than allowing a continued struggle. We sought to determine if CEW exposure on exhausted humans caused worsening acidosis when compared with continued exertion. This was a prospective study of human volunteers recruited during a CEW training course. Volunteers were from several different occupations and represented a wide range of ages and body mass index characteristics. Medical histories, baseline pH and lactate values were obtained. Patients were assigned to one of four groups: 2 control groups consisting of Exertion only and CEW Exposure only, and the 2 experimental groups that were Exertion plus CEW Exposure and Exertion plus additional Exertion. Blood sampling occurred after Exertion and after any CEW exposure. This was repeated every 2-min until 20 min after protocol completion. Descriptive statistics were used to compare the four groups. The experimental groups and the control groups were compared individually at each time point using Wilcoxon rank sum tests. Lactate and pH association was assessed using multiple linear regression. Forty subjects were enrolled. There were no median pH or lactate differences between CEW Exposure groups at baseline, or between Exertion protocol groups immediately after completion. The CEW Exposure only group had higher pH and lower lactate values at all time points after exposure than the Exertion only group. After completing the Exertion protocol, there was no difference in the pH or lactate values between the continued Exertion group and the CEW Exposure group at any time points. Subjects who had CEW Exposure only had higher pH and lower lactate values than subjects who completed the Exertion protocol only. CEW exposure does not appear to worsen acidosis in exhausted subjects any differently than briefly continued exertion.

Physical disability, life stress, and psychosocial adjustment in multiple sclerosis.

PubMed

Zeldow, P B; Pavlou, M

1984-02-01

Eighty-one outpatients with diagnosed multiple sclerosis were studied in an effort to examine the relative contributions of physical health status, life stress, duration of illness, age, sex, marital status, and social class on various aspects of personal and interpersonal functioning. Stepwise multiple regression analyses were performed to identify the most significant discriminators of the seven psychosocial measures. Physical health status exerted the broadest influence, affecting personal efficiency and well-being, capacity for independent thought and action, self-confidence, self-reliance, and number of meaningful social contacts. Life stress was associated with lowered personal efficiency and sense of well-being. Duration of illness and the demographic variables had few or no effects on psychosocial adjustment. Discussion contrasts the present findings with others in the rehabilitation literature and specifies certain limitations of the study's design.

The differential effects of gratitude and sleep on psychological distress in patients with chronic pain.

PubMed

Ng, Mei-Yee; Wong, Wing-Sze

2013-02-01

This study aimed to examine the possible cross-sectional mediating role of sleep in the relationship of gratitude with depression and anxiety in patients with chronic pain. A total of 224 patients with chronic pain completed structured questionnaires assessing chronic pain, depression and anxiety symptoms, gratitude, and sleep disturbances. Results of multiple regression analyses yielded a modest mediating effect for sleep on the gratitude-depression link whereas a stronger mediating effect was found for sleep on the gratitude-anxiety link. These data show much of the effect of gratitude on depression was direct whereas sleep exerted a stronger mediating effect on the gratitude-anxiety link.

Atheroprotective potentials of curcuminoids against ginger extract in hypercholesterolaemic rabbits.

PubMed

Elseweidy, M M; Younis, N N; Elswefy, S E; Abdallah, F R; El-Dahmy, S I; Elnagar, G; Kassem, H M

2015-01-01

The anti-atherogenic potentials of total ginger (Zingiber officinale) extract (TGE) or curcuminoids extracted from turmeric (Curcuma longa), members of family Zingiberaceae, were compared in hypercholesterolaemia. Rabbits were fed either normal or atherogenic diet. The rabbits on atherogenic diet received treatments with TGE or curcumenoids and placebo concurrently for 6 weeks (n = 6). The anti-atherogenic effects of curcuminoids and ginger are mediated via multiple mechanisms. This effect was correlated with their ability to lower cholesteryl ester transfer protein activity. Ginger extract exerted preferential effects on plasma lipids, reverse cholesterol transport, cholesterol synthesis and inflammatory status. Curcuminoids, however, showed superior antioxidant activity.

Alternative source of stem cells derived from human periodontal ligament: a new treatment for experimental autoimmune encephalomyelitis.

PubMed

Trubiani, Oriana; Giacoppo, Sabrina; Ballerini, Patrizia; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela

2016-01-04

Multiple sclerosis is a demyelinating disease mostly of autoimmune origin that affects and damages the central nervous system, leading to a disabling condition. The aim of the present study was to investigate whether administration of mesenchymal stem cells from human periodontal ligament (hPDLSCs) could ameliorate multiple sclerosis progression by exerting neuroprotective effects in an experimental model of autoimmune encephalomyelitis (EAE). EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55 in C57BL/6 mice. After immunization, mice were observed every 48 hours for signs of EAE and weight loss. At the onset of disease, approximately 14 days after immunization, EAE mice were subjected to a single intravenous injection of hPDLSCs (10(6) cells/150 μl) into the tail vein. At the point of animal sacrifice on day 56 after EAE induction, spinal cord and brain tissues were collected in order to perform histological evaluation, immunohistochemistry and western blotting analysis. Achieved results reveal that treatment with hPDLSCs may exert neuroprotective effects against EAE, diminishing both clinical signs and histological score typical of the disease (lymphocytic infiltration and demyelination) probably through the production of neurotrophic factors (results focused on brain-derived neurotrophic factor and nerve growth factor expression). Furthermore, administration of hPDLSCs modulates expression of inflammatory key markers (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, glial fibrillary acidic protein, Nrf2 and Foxp3), the release of CD4 and CD8α T cells, and the triggering of apoptotic death pathway (data shown for cleaved caspase 3, p53 and p21). In light of the achieved results, transplantation of hPDLSCs may represent a putative novel and helpful tool for multiple sclerosis treatment. These cells could have considerable implication for future therapies for multiple sclerosis and this study may represent the starting point for further investigations.

Predicting the synergy of multiple stress effects

NASA Astrophysics Data System (ADS)

Liess, Matthias; Foit, Kaarina; Knillmann, Saskia; Schäfer, Ralf B.; Liess, Hans-Dieter

2016-09-01

Toxicants and other, non-chemical environmental stressors contribute to the global biodiversity crisis. Examples include the loss of bees and the reduction of aquatic biodiversity. Although non-compliance with regulations might be contributing, the widespread existence of these impacts suggests that for example the current approach of pesticide risk assessment fails to protect biodiversity when multiple stressors concurrently affect organisms. To quantify such multiple stress effects, we analysed all applicable aquatic studies and found that the presence of environmental stressors increases individual sensitivity to toxicants (pesticides, trace metals) by a factor of up to 100. To predict this dependence, we developed the “Stress Addition Model” (SAM). With the SAM, we assume that each individual has a general stress capacity towards all types of specific stress that should not be exhausted. Experimental stress levels are transferred into general stress levels of the SAM using the stress-related mortality as a common link. These general stress levels of independent stressors are additive, with the sum determining the total stress exerted on a population. With this approach, we provide a tool that quantitatively predicts the highly synergistic direct effects of independent stressor combinations.

UV-A radiation effects on higher plants: Exploring the known unknown.

PubMed

Verdaguer, Dolors; Jansen, Marcel A K; Llorens, Laura; Morales, Luis O; Neugart, Susanne

2017-02-01

Ultraviolet-A radiation (UV-A: 315-400nm) is a component of solar radiation that exerts a wide range of physiological responses in plants. Currently, field attenuation experiments are the most reliable source of information on the effects of UV-A. Common plant responses to UV-A include both inhibitory and stimulatory effects on biomass accumulation and morphology. UV-A effects on biomass accumulation can differ from those on root: shoot ratio, and distinct responses are described for different leaf tissues. Inhibitory and enhancing effects of UV-A on photosynthesis are also analysed, as well as activation of photoprotective responses, including UV-absorbing pigments. UV-A-induced leaf flavonoids are highly compound-specific and species-dependent. Many of the effects on growth and development exerted by UV-A are distinct to those triggered by UV-B and vary considerably in terms of the direction the response takes. Such differences may reflect diverse UV-perception mechanisms with multiple photoreceptors operating in the UV-A range and/or variations in the experimental approaches used. This review highlights a role that various photoreceptors (UVR8, phototropins, phytochromes and cryptochromes) may play in plant responses to UV-A when dose, wavelength and other conditions are taken into account. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bivalent compound 17MN exerts neuroprotection through interaction at multiple sites in a cellular model of Alzheimer’s disease

PubMed Central

Liu, Kai; Chojnacki, Jeremy E.; Wade, Emily E.; Saathoff, John M.; Lesnefsky, Edward J.; Chen, Qun; Zhang, Shijun

2016-01-01

Multiple pathogenic factors have been suggested in playing a role in the development of Alzheimer’s disease (AD). The multifactorial nature of AD also suggests the potential use of compounds with polypharmacology as effective disease-modifying agents. Recently, we have developed a bivalent strategy to include cell membrane anchorage into the molecular design. Our results demonstrated that the bivalent compounds exhibited multifunctional properties and potent neuroprotection in a cellular AD model. Herein, we report the mechanistic exploration of one of the representative bivalent compounds, 17MN, in MC65 cells. Our results established that MC65 cells die through a necroptotic mechanism upon the removal of tetracycline (TC). Furthermore, we have shown that mitochondrial membrane potential (MMP) and cytosolic Ca2+ levels are increased upon removal of TC. Our bivalent compound 17MN can reverse such changes and protect MC65 cells from TC removal induced cytotoxicity. The results also suggest that 17MN may function between the Aβ species and RIPK1 in producing its neuroprotection. Colocalization studies employing a fluorescent analog of 17MN and confocal microscopy demonstrated the interactions of 17MN with both mitochondria and endoplasmic reticulum (ER), thus suggesting that 17MN exerts its neuroprotection via a multiple-site mechanism in MC65 cells. Collectively, these results strongly support our original design rationale of bivalent compounds and encourage further optimization of this bivalent strategy to develop more potent analogs as novel disease-modifying agents for AD. PMID:26401780

Musical agency reduces perceived exertion during strenuous physical performance

PubMed Central

Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

2013-01-01

Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting. PMID:24127588

Musical agency reduces perceived exertion during strenuous physical performance.

PubMed

Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

2013-10-29

Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting.

Stress Underestimation and Mental Health Outcomes in Male Japanese Workers: a 1-Year Prospective Study.

PubMed

Izawa, Shuhei; Nakamura-Taira, Nanako; Yamada, Kosuke Chris

2016-12-01

Being appropriately aware of the extent of stress experienced in daily life is essential in motivating stress management behaviours. Excessive stress underestimation obstructs this process, which is expected to exert adverse effects on health. We prospectively examined associations between stress underestimation and mental health outcomes in Japanese workers. Web-based surveys were conducted twice with an interval of 1 year on 2359 Japanese male workers. Participants were asked to complete survey items concerning stress underestimation, depressive symptoms, sickness absence, and antidepressant use. Multiple logistic regression analysis revealed that high baseline levels of 'overgeneralization of stress' and 'insensitivity to stress' were significantly associated with new-onset depressive symptoms (OR = 2.66 [95 % CI, 1.54-4.59], p < .01) and antidepressant use (OR = 4.91 [95 % CI, 1.22-19.74], p < .05), respectively, during the 1-year follow-up period. This study clearly demonstrated that stress underestimation, including stress insensitivity and the overgeneralization of stress, could exert adverse effects on mental health.

The interactions of multisensory integration with endogenous and exogenous attention

PubMed Central

Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

2016-01-01

Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. PMID:26546734

The interactions of multisensory integration with endogenous and exogenous attention.

PubMed

Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

2016-02-01

Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

PubMed

Hsieh, Chia-Jung; Hsu, Ya-Ling; Huang, Ya-Fang; Tsai, Eing-Mei

2018-01-01

Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fluoxetine exposure impacts boldness in female Siamese fighting fish, Betta splendens.

PubMed

Dzieweczynski, Teresa L; Kane, Jessica L; Campbell, Brennah A; Lavin, Lindsey E

2016-01-01

The present study examined the effects of the selective serotonin reuptake inhibitor, fluoxetine, on the behavior of female Siamese fighting fish, Betta splendens, in three different boldness assays (Empty Tank, Novel Environment, Social Tendency). When females were unexposed to fluoxetine, boldness was consistent within a context and correlated across assays. Fluoxetine exposure affected behavior within and among individuals on multiple levels. Exposure reduced overall boldness levels, made females behave in a less consistent manner, and significantly reduced correlations over time and across contexts. Fluoxetine exerted its effects on female Betta splendens behavior in a dose-dependent fashion and these effects persisted even after females were housed in clean water. If fluoxetine exposure impacts behaviors such as exploration that are necessary to an individual’s success, this may yield evolutionary consequences. In conclusion, the results show that fluoxetine exposure alters behavior beyond the level of overall response and highlights the importance of studying the behavioral effects of inadvertent pharmaceutical exposure in multiple contexts and with different dosing regimes.

Evaluation of Antioxidant Potential of “Maltese Mushroom” (Cynomorium coccineum) by Means of Multiple Chemical and Biological Assays

PubMed Central

Zucca, Paolo; Rosa, Antonella; Tuberoso, Carlo I. G.; Piras, Alessandra; Rinaldi, Andrea C.; Sanjust, Enrico; Dessì, Maria A.; Rescigno, Antonio

2013-01-01

Cynomorium coccineum is an edible, non-photosynthetic plant widespread along the coasts of the Mediterranean Sea. The medicinal properties of Maltese mushroom—one of the oldest vernacular names used to identify this species—have been kept in high regard since ancient times to the present day. We evaluated the antioxidant potential of fresh specimens of C. coccineum picked in Sardinia, Italy. Both aqueous and methanolic extracts were tested by using multiple assay systems (DPPH, FRAP, TEAC, ORAC-PYR). Total phenolics and flavonoids were also determined. Gallic acid and cyanidin 3-O-glucoside were identified as the main constituents and measured. Both extracts showed antioxidant capacities; ORAC-PYR assay gave the highest antioxidant value in both cases. The methanolic extract was further investigated with in vitro biological models of lipid oxidation; it showed a significant activity in preventing cholesterol degradation and exerted protection against Cu2+-mediated degradation of the liposomal unsaturated fatty acids. Results of the present study demonstrate that the extracts of C. coccineum show a significant total antioxidant power and also exert an in vitro protective effect in different bio-assays of oxidative stress. Therefore, Maltese mushroom can be considered a valuable source of antioxidants and phytochemicals useful in the preparation of nutraceuticals and functional foods. PMID:23344249

The role of acetylcholine in cocaine addiction.

PubMed

Williams, Mark J; Adinoff, Bryon

2008-07-01

Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study.

PubMed

Milosević, Verica Lj; Stevanović, Darko M; Nesić, Dejan M; Sosić-Jurjević, Branka T; Ajdzanović, Vladimir Z; Starcević, Vesna P; Severs, Walter B

2010-06-01

Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 microl phosphate buffered saline with or without 1 microg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p<0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p<0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p<0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic unbalance effects, remains a very important research goal.

The Role of Cell Surface Architecture of Lactobacilli in Host-Microbe Interactions in the Gastrointestinal Tract

PubMed Central

Altermann, Eric; Anderson, Rachel C.; McNabb, Warren C.; Moughan, Paul J.; Roy, Nicole C.

2013-01-01

Lactobacillus species can exert health promoting effects in the gastrointestinal tract (GIT) through many mechanisms, which include pathogen inhibition, maintenance of microbial balance, immunomodulation, and enhancement of the epithelial barrier function. Different species of the genus Lactobacillus can evoke different responses in the host, and not all strains of the same species can be considered beneficial. Strain variations may be related to diversity of the cell surface architecture of lactobacilli and the bacteria's ability to express certain surface components or secrete specific compounds in response to the host environment. Lactobacilli are known to modify their surface structures in response to stress factors such as bile and low pH, and these adaptations may help their survival in the face of harsh environmental conditions encountered in the GIT. In recent years, multiple cell surface-associated molecules have been implicated in the adherence of lactobacilli to the GIT lining, immunomodulation, and protective effects on intestinal epithelial barrier function. Identification of the relevant bacterial ligands and their host receptors is imperative for a better understanding of the mechanisms through which lactobacilli exert their beneficial effects on human health. PMID:23576850

Stimulatory versus suppressive effects of GM-CSF on tumor progression in multiple cancer types

PubMed Central

Hong, In-Sun

2016-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF, also called CSF-2) is best known for its critical role in immune modulation and hematopoiesis. A large body of experimental evidence indicates that GM-CSF, which is frequently upregulated in multiple types of human cancers, effectively marks cancer cells with a ‘danger flag' for the immune system. In this context, most studies have focused on its function as an immunomodulator, namely its ability to stimulate dendritic cell (DC) maturation and monocyte/macrophage activity. However, recent studies have suggested that GM-CSF also promotes immune-independent tumor progression by supporting tumor microenvironments and stimulating tumor growth and metastasis. Although some studies have suggested that GM-CSF has inhibitory effects on tumor growth and metastasis, an even greater number of studies show that GM-CSF exerts stimulatory effects on tumor progression. In this review, we summarize a number of findings to provide the currently available information regarding the anticancer immune response of GM-CSG. We then discuss the potential roles of GM-CSF in the progression of multiple types of cancer to provide insights into some of the complexities of its clinical applications. PMID:27364892

On the nonlinear dynamics of trolling-mode AFM: Analytical solution using multiple time scales method

NASA Astrophysics Data System (ADS)

Sajjadi, Mohammadreza; Pishkenari, Hossein Nejat; Vossoughi, Gholamreza

2018-06-01

Trolling mode atomic force microscopy (TR-AFM) has resolved many imaging problems by a considerable reduction of the liquid-resonator interaction forces in liquid environments. The present study develops a nonlinear model of the meniscus force exerted to the nanoneedle of TR-AFM and presents an analytical solution to the distributed-parameter model of TR-AFM resonator utilizing multiple time scales (MTS) method. Based on the developed analytical solution, the frequency-response curves of the resonator operation in air and liquid (for different penetration length of the nanoneedle) are obtained. The closed-form analytical solution and the frequency-response curves are validated by the comparison with both the finite element solution of the main partial differential equations and the experimental observations. The effect of excitation angle of the resonator on horizontal oscillation of the probe tip and the effect of different parameters on the frequency-response of the system are investigated.

Reversible electrical-field control of magnetization and anomalous Hall effect in Co/PMN-PT hybrid heterostructures

NASA Astrophysics Data System (ADS)

Wang, J.; Huang, Q. K.; Lu, S. Y.; Tian, Y. F.; Chen, Y. X.; Bai, L. H.; Dai, Y.; Yan, S. S.

2018-04-01

Room-temperature reversible electrical-field control of the magnetization and the anomalous Hall effect was reported in hybrid multiferroic heterojunctions based on Co/Pb(Mg1/3Nb2/3)0.7Ti0.3O3 (PMN-PT). We demonstrate herein that electrical-field-induced strain and oxygen-ion migration in ZnO/Co/PMN-PT junctions exert opposing effects on the magnetic properties of the Co sublayer, and the competition between these effects determines the final magnitude of magnetization. This proof-of-concept investigation opens an alternative way to optimize and enhance the electrical-field effect on magnetism through the combination of multiple electrical manipulation mechanisms in hybrid multiferroic devices.

Flexible random lasers with tunable lasing emissions.

PubMed

Lee, Ya-Ju; Chou, Chun-Yang; Yang, Zu-Po; Nguyen, Thi Bich Hanh; Yao, Yung-Chi; Yeh, Ting-Wei; Tsai, Meng-Tsan; Kuo, Hao-Chun

2018-04-19

In this study, we experimentally demonstrated a flexible random laser fabricated on a polyethylene terephthalate (PET) substrate with a high degree of tunability in lasing emissions. Random lasing oscillation arises mainly from the resonance coupling between the emitted photons of gain medium (Rhodamine 6G, R6G) and the localized surface plasmon (LSP) of silver nanoprisms (Ag NPRs), which increases the effective cross-section for multiple light scattering, thus stimulating the lasing emissions. More importantly, it was found that the random lasing wavelength is blue-shifted monolithically with the increase in bending strains exerted on the PET substrate, and a maximum shift of ∼15 nm was achieved in the lasing wavelength, when a 50% bending strain was exerted on the PET substrate. Such observation is highly repeatable and reversible, and this validates that we can control the lasing wavelength by simply bending the flexible substrate decorated with the Ag NPRs. The scattering spectrum of the Ag NPRs was obtained using a dark-field microscope to understand the mechanism for the dependence of the wavelength shift on the exerted bending strains. As a result, we believe that the experimental demonstration of tunable lasing emissions based on the revealed structure is expected to open up a new application field of random lasers.

Sulfur dioxide: foe or friend for life?

PubMed

Wang, Xin-Bao; Cui, Hong; Liu, Xiaohong; Du, Jun-Bao

2017-12-01

Sulfur dioxide (SO₂) is a toxic gas and air pollutant. The toxic effects of SO₂ have been extensively studied. Oxidative damage due to SO₂ can occur in multiple organs. Inhaled SO₂ can also cause chromosomal aberrations, DNA damage and gene mutations in mammals. However, SO₂ can also be generated from the sulfur-containing amino acid, L-cysteine. Recent studies have shown that SO₂ has a vasorelaxant effect, and ameliorates pulmonary hypertension and vascular remodeling. SO₂ can also reduce lung injury and myocardial injury in rats. In addition, SO₂ reduces myocardial ischemia-reperfusion injury and atherosclerotic lesions. Therefore, SO₂ exerts both detrimental and protective effects in mammals. Is SO₂ a foe or friend for life?.

PDE4 as a target for cognition enhancement

PubMed Central

Richter, Wito; Menniti, Frank S.; Zhang, Han-Ting; Conti, Marco

2014-01-01

Introduction The second messengers cAMP and cGMP mediate fundamental aspects of brain function relevant to memory, learning and cognitive functions. Consequently, cyclic nucleotide phosphodiesterases (PDEs), the enzymes that inactivate the cyclic nucleotides, are promising targets for the development of cognition-enhancing drugs. Areas covered PDE4 is the largest of the eleven mammalian PDE families. This review covers the properties and functions of the PDE4 family, highlighting procognitive and memory-enhancing effects associated with their inactivation. Expert opinion PAN-selective PDE4 inhibitors exert a number of memory- and cognition-enhancing effects and have neuroprotective and neuroregenerative properties in preclinical models. The major hurdle for their clinical application is to target inhibitors to specific PDE4 isoforms relevant to particular cognitive disorders to realize the therapeutic potential while avoiding side effects, in particular emesis and nausea. The PDE4 family comprises four genes, PDE4A-D, each expressed as multiple variants. Progress to date stems from characterization of rodent models with selective ablation of individual PDE4 subtypes, revealing that individual subtypes exert unique and non-redundant functions in the brain. Thus, targeting specific PDE4 subtypes, as well as splicing variants or conformational states, represents a promising strategy to separate the therapeutic benefits from the side effects of PAN-PDE4 inhibitors. PMID:23883342

Topical Anti-Inflammatory and Analgesic Effects of Multiple Applications of S(+)-Flurbiprofen Plaster (SFPP) in a Rat Adjuvant-Induced Arthritis Model.

PubMed

Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-06-01

Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)-flurbiprofen plaster (SFPP), a novel Nonsteroidal anti-inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant-induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)-1 and COX-2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti-inflammatory effects clinically. Drug Dev Res 77 : 206-211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

Topical Anti‐Inflammatory and Analgesic Effects of Multiple Applications of S(+)‐Flurbiprofen Plaster (SFPP) in a Rat Adjuvant‐Induced Arthritis Model

PubMed Central

Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-01-01

Abstract Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)‐flurbiprofen plaster (SFPP), a novel Nonsteroidal anti‐inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant‐induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)−1 and COX‐2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti‐inflammatory effects clinically. Drug Dev Res 77 : 206–211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc. PMID:27241582

Effect of physical exercise on brain and lipid metabolism in mouse models of multiple sclerosis.

PubMed

Houdebine, Léo; Gallelli, Cristina Anna; Rastelli, Marialetizia; Sampathkumar, Nirmal Kumar; Grenier, Julien

2017-10-01

Multiple sclerosis (MS) is a central nervous demyelinating disease characterized by cyclic loss and repair of myelin sheaths associated with chronic inflammation and neuronal loss. This degenerative pathology is accompanied by modified levels of oxysterols (oxidative derivatives of cholesterol, implicated in cholesterol metabolism), highlighted in the brain, blood and cerebrospinal fluid of MS patients. The pathological accumulation of such derivatives is thought to participate in the onset and progression of the disease through their implication in inflammation, oxidative stress, demyelination and neurodegeneration. In this context, physical exercise is envisaged as a complementary resource to ameliorate therapeutic strategies. Indeed, physical activity exerts beneficial effects on neuronal plasticity, decreases inflammation and oxidative stress and improves blood-brain integrity in extents that could be beneficial for brain health. The present review attempts to summarize the available data on the positive effect of physical exercise to highlight possible links between physical activity and modulation of cholesterol/oxysterol homeostasis in MS. Copyright © 2017 Elsevier B.V. All rights reserved.

PREDICTION OF VO2PEAK USING OMNI RATINGS OF PERCEIVED EXERTION FROM A SUBMAXIMAL CYCLE EXERCISE TEST

PubMed Central

Mays, Ryan J.; Goss, Fredric L.; Nagle-Stilley, Elizabeth F.; Gallagher, Michael; Schafer, Mark A.; Kim, Kevin H.; Robertson, Robert J.

2015-01-01

Summary The primary aim of this study was to develop statistical models to predict peak oxygen consumption (VO2peak) using OMNI Ratings of Perceived Exertion measured during submaximal cycle ergometry. Men (mean ± standard error: 20.90 ± 0.42 yrs) and women (21.59 ± 0.49 yrs) participants (n = 81) completed a load-incremented maximal cycle ergometer exercise test. Simultaneous multiple linear regression was used to develop separate VO2peak statistical models using submaximal ratings of perceived exertion for the overall body, legs, and chest/breathing as predictor variables. VO2peak (L·min−1) predicted for men and women from ratings of perceived exertion for the overall body (3.02 ± 0.06; 2.03 ± 0.04), legs (3.02 ± 0.06; 2.04 ± 0.04) and chest/breathing (3.02 ± 0.05; 2.03 ± 0.03) were similar with measured VO2peak (3.02 ± 0.10; 2.03 ± 0.06, ps > .05). Statistical models based on submaximal OMNI Ratings of Perceived Exertion provide an easily administered and accurate method to predict VO2peak. PMID:25068750

Effect of physical workload and modality of information presentation on pattern recognition and navigation task performance by high-fit young males.

PubMed

Zahabi, Maryam; Zhang, Wenjuan; Pankok, Carl; Lau, Mei Ying; Shirley, James; Kaber, David

2017-11-01

Many occupations require both physical exertion and cognitive task performance. Knowledge of any interaction between physical demands and modalities of cognitive task information presentation can provide a basis for optimising performance. This study examined the effect of physical exertion and modality of information presentation on pattern recognition and navigation-related information processing. Results indicated males of equivalent high fitness, between the ages of 18 and 34, rely more on visual cues vs auditory or haptic for pattern recognition when exertion level is high. We found that navigation response time was shorter under low and medium exertion levels as compared to high intensity. Navigation accuracy was lower under high level exertion compared to medium and low levels. In general, findings indicated that use of the haptic modality for cognitive task cueing decreased accuracy in pattern recognition responses. Practitioner Summary: An examination was conducted on the effect of physical exertion and information presentation modality in pattern recognition and navigation. In occupations requiring information presentation to workers, who are simultaneously performing a physical task, the visual modality appears most effective under high level exertion while haptic cueing degrades performance.

New perspectives of curcumin in cancer prevention

PubMed Central

Park, Wungki; Amin, A.R.M Ruhul; Chen, Zhuo Georgia; Shin, Dong M.

2013-01-01

Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. PMID:23466484

Prior Acute Mental Exertion in Exercise and Sport

PubMed Central

Silva-Júnior, Fernando Lopes e; Emanuel, Patrick; Sousa, Jordan; Silva, Matheus; Teixeira, Silmar; Pires, Flávio Oliveira; Machado, Sérgio; Arias-Carrion, Oscar

2016-01-01

Introduction: Mental exertion is a psychophysiological state caused by sustained and prolonged cognitive activity. The understanding of the possible effects of acute mental exertion on physical performance, and their physiological and psychological responses are of great importance for the performance of different occupations, such as military, construction workers, athletes (professional or recreational) or simply practicing regular exercise, since these occupations often combine physical and mental tasks while performing their activities. However, the effects of implementation of a cognitive task on responses to aerobic exercise and sports are poorly understood. Our narrative review aims to provide information on the current research related to the effects of prior acute mental fatigue on physical performance and their physiological and psychological responses associated with exercise and sports. Methods: The literature search was conducted using the databases PubMed, ISI Web of Knowledge and PsycInfo using the following terms and their combinations: “mental exertion”, “mental fatigue”, “mental fatigue and performance”, “mental exertion and sports” “mental exertion and exercise”. Results: We concluded that prior acute mental exertion affects effectively the physiological and psychophysiological responses during the cognitive task, and performance in exercise. Conclusion: Additional studies involving prior acute mental exertion, exercise/sports and physical performance still need to be carried out in order to analyze the physiological, psychophysiological and neurophysiological responses subsequently to acute mental exertion in order to identify cardiovascular factors, psychological, neuropsychological associates. PMID:27867415

Enhancement of antitumor activity of OK-432 (picibanil) by Triton X-114 phase partitioning.

PubMed

Hashimoto, Masahito; Takashige, Katsuhiro; Furuyashiki, Maiko; Yoshidome, Keitaro; Sano, Ryoko; Kawamura, Yutaka; Ijichi, Shinji; Morioka, Hirofumi; Koide, Hiroyuki; Oku, Naoto; Moriya, Yoichiro; Kusumoto, Shoich; Suda, Yasuo

2008-01-01

OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for immunotherapy of various cancers as a biological response modifier (BRM). However, OK-432 contains multiple components consisting of immunotherapeutic ones and contaminants which may weaken the effects or exert side-effects. In this study, we investigated extraction of contaminants from OK-432 using Triton X-114 (TX-114)-water phase partitioning and examined an antitumor effect of the resulting preparation. OK-432 was subjected to TX-114 partitioning to give residual precipitate designated as OK-TX-ppt. OK-TX-ppt exerted no TLR2-mediated activity, but induced interleukin (IL)-6 in human PBMC. OK-TX-ppt also induced tumor necrosis factor (TNF)-alpha, IL-10, IL-12, and interferon (IFN)-gamma in PBMC. Moreover, IFN-gamma-inducing activity of OK-TX-ppt was significantly higher and IL-10 production was lower than that of OK-432. In tumor-bearing mice model, administration of OK-TX-ppt i.p. extended the survival time of Meth-A-bearing mice compared to OK-432. OK-TX-ppt also increased the levels of IL-12 and IFN-gamma in mouse spleen cells in vitro. These results indicated that TX-114 partitioning removed some contaminants, which attenuates the antitumor effect, from OK-432 and increase the immunotherapeutic effects of OK-432.

Fast computation of radiation pressure force exerted by multiple laser beams on red blood cell-like particles

NASA Astrophysics Data System (ADS)

Gou, Ming-Jiang; Yang, Ming-Lin; Sheng, Xin-Qing

2016-10-01

Mature red blood cells (RBC) do not contain huge complex nuclei and organelles, makes them can be approximately regarded as homogeneous medium particles. To compute the radiation pressure force (RPF) exerted by multiple laser beams on this kind of arbitrary shaped homogenous nano-particles, a fast electromagnetic optics method is demonstrated. In general, based on the Maxwell's equations, the matrix equation formed by the method of moment (MOM) has many right hand sides (RHS's) corresponding to the different laser beams. In order to accelerate computing the matrix equation, the algorithm conducts low-rank decomposition on the excitation matrix consisting of all RHS's to figure out the so-called skeleton laser beams by interpolative decomposition (ID). After the solutions corresponding to the skeletons are obtained, the desired responses can be reconstructed efficiently. Some numerical results are performed to validate the developed method.

Recent advances in the study on capsaicinoids and capsinoids.

PubMed

Luo, Xiu-Ju; Peng, Jun; Li, Yuan-Jian

2011-01-10

Chili peppers are the major source of nature capsaicinoids, which consist of capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin, etc. Capsaicinoids are found to exert multiple pharmacological and physiological effects including the activities of analgesia, anticancer, anti-inflammation, antioxidant and anti-obesity. Therefore, capsaicinoids may have the potential value in clinic for pain relief, cancer prevention and weight loss. In addition, capsaicinoids also display the benefits on cardiovascular and gastrointestinal system. It has been shown that capsaicinoids are potential agonists of capsaicin receptor or transient receptor potential vanilloid subfamily member 1 (TRPV1). They could exert the effects not only through the receptor-dependent pathway but also through the receptor-independent one. CH-19 Sweet peppers are the source of nature capsinoids, which share similar structure with capsaicinoids and consist of capsiate, dihydrocapsiate, and nordihydrocapsiate, etc, Comparing with capsaicinoids, capsinoids are less pungent and easily broken down in the normal aqueous conditions. So far, it has been found that capsinoids possess the biological properties of antitumor, antioxidant and anti-obesity. Since capsinoids are less toxic than capsaicinoids, therefore, capsinoids may have the advantages over capsaicinoids in clinical applications such as cancer prevention and weight loss. Copyright © 2010 Elsevier B.V. All rights reserved.

hCG and Its Disruption by Environmental Contaminants during Human Pregnancy

PubMed Central

Paulesu, Luana; Rao, Ch.V.; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

2018-01-01

Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances. PMID:29558393

hCG and Its Disruption by Environmental Contaminants during Human Pregnancy.

PubMed

Paulesu, Luana; Rao, Ch V; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

2018-03-20

Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para -Nonylphenol ( p -NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances.

Don't abandon hope all ye who enter here: The protective role of formal mentoring and learning processes on burnout in correctional officers.

PubMed

Farnese, M L; Barbieri, B; Bellò, B; Bartone, P T

2017-01-01

Within a Job Demands-Resources Model framework, formal mentoring can be conceived as a job resource expressing the organization's support for new members, which may prevent their being at risk for burnout. This research aims at understanding the protective role of formal mentoring on burnout, through the effect of increasing learning personal resources. Specifically, we hypothesized that formal mentoring enhances newcomers' learning about job and social domains related to the new work context, thus leading to lower burnout. In order to test the hypotheses, a multiple regression analysis using the bootstrapping method was used. Based on a questionnaire administered to 117 correctional officer newcomers who had a formal mentor assigned, our results confirm that formal mentoring exerts a positive influence on newcomers' adjustment, and that this in turn exerts a protective influence against burnout onset by reducing cynicism and interpersonal stress and also enhancing the sense of personal accomplishment. Confirming previous literature's suggestions, supportive mentoring and effective socialization seem to represent job and personal resources that are protective against burnout. This study provides empirical support for this relation in the prison context.

The physiological basis of complementary and alternative medicines for polycystic ovary syndrome.

PubMed

Raja-Khan, Nazia; Stener-Victorin, Elisabet; Wu, XiaoKe; Legro, Richard S

2011-07-01

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by chronic hyperandrogenic anovulation leading to symptoms of hirsutism, acne, irregular menses, and infertility. Multiple metabolic and cardiovascular risk factors are associated with PCOS, including insulin resistance, obesity, type 2 diabetes, hypertension, inflammation, and subclinical atherosclerosis. However, current treatments for PCOS are only moderately effective at controlling symptoms and preventing complications. This article describes how the physiological effects of major complementary and alternative medicine (CAM) treatments could reduce the severity of PCOS and its complications. Acupuncture reduces hyperandrogenism and improves menstrual frequency in PCOS. Acupuncture's clinical effects are mediated via activation of somatic afferent nerves innervating the skin and muscle, which, via modulation of the activity in the somatic and autonomic nervous system, may modulate endocrine and metabolic functions in PCOS. Chinese herbal medicines and dietary supplements may also exert beneficial physiological effects in PCOS, but there is minimal evidence that these CAM treatments are safe and effective. Mindfulness has not been investigated in PCOS, but it has been shown to reduce psychological distress and exert positive effects on the central and autonomic nervous systems, hypothalamic-pituitary-adrenal axis, and immune system, leading to reductions in blood pressure, glucose, and inflammation. In conclusion, CAM treatments may have beneficial endocrine, cardiometabolic, and reproductive effects in PCOS. However, most studies of CAM treatments for PCOS are small, nonrandomized, or uncontrolled. Future well-designed studies are needed to further evaluate the safety, effectiveness, and mechanisms of CAM treatments for PCOS.

Lactoferricin mediates anabolic and anti-catabolic effects in the intervertebral disc.

PubMed

Kim, Jae-Sung; Ellman, Michael B; An, Howard S; Yan, Dongyao; van Wijnen, Andre J; Murphy, Gillian; Hoskin, David W; Im, Hee-Jeong

2012-04-01

Lactoferricin (LfcinB) antagonizes biological effects mediated by angiogenic and catabolic growth factors, in addition to pro-inflammatory cytokines and chemokines in human endothelial cells and tumor cells. However, the effect of LfcinB on intervertebral disc (IVD) cell metabolism has not yet been investigated. Using bovine nucleus pulposus (NP) cells, we analyzed the effect of LfcinB on proteoglycan (PG) accumulation, PG synthesis, and anabolic gene expression. We assessed expression of genes for matrix-degrading enzymes such as matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family), as well as their endogenous inhibitors, tissue inhibitor of metalloproteases (TIMPs). In order to understand the specific molecular mechanisms by which LfcinB exerts its biological effects, we investigated intracellular signaling pathways in NP cells. LfcinB increased PG accumulation mainly via PG synthesis in a dose-dependent manner. Simultaneously, LfcinB dose-dependently downregulated catabolic enzymes. LfcinB's anti-catabolic effects were further demonstrated by a dose-dependent increase in multiple TIMP family members. Our results demonstrate that ERK and/or p38 mitogen-activated protein kinase pathways are the key signaling cascades that exert the biological effects of LfcinB in NP cells, regulating transcription of aggrecan, SOX-9, TIMP-1, TIMP-2, TIMP-3, and iNOS. Our results suggest that LfcinB has anabolic and potent anti-catabolic biological effects on bovine IVD cells that may have considerable promise in the treatment of disc degeneration in the future. Copyright © 2011 Wiley Periodicals, Inc.

The Molecular Links of Re-Emerging Therapy: A Review of Evidence of Brahmi (Bacopa monniera)

PubMed Central

Mathur, Deepali; Goyal, Kritika; Koul, Veena; Anand, Akshay

2016-01-01

The convolution associated with memory is being resolved with advancement in neuroscience. According to the concurrent assumptions, synaptic plasticity forms one of the basis of memory formation, stabilization and strengthening. In Alzheimer's disease (AD), which is generally characterized by memory dysfunction, connections amongst the cells in the brain are attenuated or lost leading to degeneration of neural networks. Numerous attempts have been made to find new therapies for memory dysfunction with increasing attention and investments being laid on herbal drugs. Many herbal plants and extracts have already documented beneficial results when tested for antiamnesic effects. Brahmi (Bacopa monniera) is one such common herbal drug, which is employed for a long time in the Indian and Chinese medical system in order to treat several disorders. Previous research has shown that Brahmi exerts many pharmacological effects including memory boosting capacity in the treatment of Alzheimer's disease and Schizophrenia, exhibiting antiparkinsonian, antistroke, and anticonvulsant potentials. The present review discusses the chemical constituents of Brahmi along with in vitro and in vivo studies based on the pharmacological effects exerted by it. The efficacy of Brahmi in treating various disorders has evoked sufficient research in recent years and now it is a time to launch multiple clinical trials. PMID:26973531

The effects of therapeutic instrumental music performance on endurance level, self-perceived fatigue level, and self-perceived exertion of inpatients in physical rehabilitation.

PubMed

Lim, Hayoung A; Miller, Karen; Fabian, Chuck

2011-01-01

The present study investigated the effects of a Neurologic Music Therapy (NMT) sensory-motor rehabilitation technique, Therapeutic Instrumental Music Performance (TIMP) as compared to Traditional Occupational Therapy (TOT), on endurance, self-perceived fatigue, and self-perceived exertion of 35 hospitalized patients in physical rehabilitation. The present study attempted to examine whether an active musical experience such as TIMP with musical cueing (i.e., rhythmic auditory cueing) during physical exercises influences one's perception of pain, fatigue, and exertion. All participants were diagnosed with a neurologic disorder or had recently undergone orthopedic surgery. Investigators measured the effects of TOT and TIMP during upper extremity exercise of the less affected or stronger upper extremity. Results showed no significant difference on endurance measures between the 2 treatment conditions (TIMP and TOT). Statistically significant differences were found between TIMP and TOT when measuring their effects on perceived exertion and perceived fatigue. TIMP resulted in significantly less perception of fatigue and exertion levels than TOT. TIMP can be used foran effective sensory-motor rehabilitation technique to decrease perceived exertion and fatigue level of inpatients in physical rehabilitation.

Interesting images: Multiple coronary artery aneurysms.

PubMed

Howard, Jonathon M; Viswanath, Omar; Armas, Alfredo; Santana, Orlando; Rosen, Gerald P

2017-01-01

We present the case of a 65-year-old male who presented with stable angina and dyspnea on exertion. His initial workup yielded a positive treadmill stress test for reversible apical ischemia, and transthoracic echocardiogram demonstrated impaired systolic function. Cardiac catheterization was then performed, revealing severe atherosclerotic disease including multiple coronary artery aneurysms. As a result, the patient was advised to and subsequently underwent a coronary artery bypass graft. This case highlights the presence of multiple coronary artery aneurysms and the ability to appreciate these pathologic findings on multiple imaging modalities, including coronary angiogram, transesophageal echocardiography, and direct visualization through the surgical field.

Interesting Images: Multiple Coronary Artery Aneurysms

PubMed Central

Howard, Jonathon M; Viswanath, Omar; Armas, Alfredo; Santana, Orlando; Rosen, Gerald P

2017-01-01

We present the case of a 65-year-old male who presented with stable angina and dyspnea on exertion. His initial workup yielded a positive treadmill stress test for reversible apical ischemia, and transthoracic echocardiogram demonstrated impaired systolic function. Cardiac catheterization was then performed, revealing severe atherosclerotic disease including multiple coronary artery aneurysms. As a result, the patient was advised to and subsequently underwent a coronary artery bypass graft. This case highlights the presence of multiple coronary artery aneurysms and the ability to appreciate these pathologic findings on multiple imaging modalities, including coronary angiogram, transesophageal echocardiography, and direct visualization through the surgical field. PMID:28701599

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

PubMed Central

Woolfrey, Kevin M.; Penzes, Peter

2013-01-01

Converging evidence from cellular, electrophysiological, anatomic, and behavioral studies suggests that the remodeling of synapse structure and function is a critical component of cognition. This modulation of neuroplasticity can be achieved through the actions of numerous extracellular signals. Moreover, it is thought that it is the integration of different extracellular signals regulation of neuroplasticity that greatly influences cognitive function. One group of signals that exerts powerful effects on multiple neurologic processes is estrogens. Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects. We discuss the potential sources and the biosynthesis of estrogens within the brain and the consequences of rapid estrogenic-signaling on the remodeling of neural circuits. Furthermore, we argue that estrogens act via distinct signaling pathways to modulate synapse structure and function in a manner that may vary with cell type, developmental stage, and sex. Finally, we present a model in which the coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits, contributing to cognition, with potential relevance for the development of novel estrogenic-based therapies for neurodevelopmental or neurodegenerative disorders. PMID:24076546

Statins and cancer.

PubMed

Vallianou, Natalia G; Kostantinou, Alexandra; Kougias, Marios; Kazazis, Christos

2014-06-01

Statins have pleiotropic properties and might exert an effect even in the field of cancer. Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, the major rate-limiting enzyme that controls the conversion of HMG-CoA to mevalonic acid. Specifically, inhibition of HMG-CoA reductase by statins has been proved to prevent the synthesis of mevalonic acid, a precursor of non-steroidal isoprenoids, which are lipid attachment molecules for small G proteins, such as Ras, Rho and Rac. Thus, statins may inhibit the synthesis of isoprenoids and thereby suppress the activation of small G proteins. In addition, statins exert pro-apoptotic, anti-angiogenic, and immunomodulatory effects, which may prevent cancer growth. Statins may inhibit the growth of a variety of cancer cell types, including breast, gastric, pancreatic, and prostate carcinoma, neuroblastoma, melanoma, mesothelioma and acute myeloid leukemia cells. They exert pro-apoptotic effects in a wide range of cancer cell lines, but with many differences in the sensitivity to statin-induced cell death among different cancer cell types. Regarding anti-angiogenic effects, multiple statin effects on blood vessel formation by inhibition of angiogenesis through down-regulation of pro-angiogenic factors, such as vascular endothelial growth factor, inhibition of endothelial cell proliferation and inhibition of adhesion to extracellular matrix by blocking intercellular adhesion molecules have been suggested. The molecular mechanisms of statin immunomodulation often implicate multiple pathways, regarding the regulation of genes encoding key molecules, which are involved in antigen presentation and subsequent immunomodulation. Another mechanism involves the down-regulation of the nuclear factor-kappa-B, which is responsible for the transcription of many genes involved in immunologic mechanisms, such as interferon-inducible protein-10, monocyte chemo-attractant protein 1 and cyclooxygenase-2. Statins have been associated with a significantly lower risk of breast, colorectal, ovarian, pancreatic, lung cancers and lymphoma in several observational studies. On the other hand, other studies, including meta-analyses have raised concerns about the safety of statins among elderly patients. A recent study upon the relationship between statin use (prior to cancer diagnosis) and cancer-related mortality in the entire Danish population from 1995-2009 in adults > 40 years of age has been conducted. As compared to statin non-users, patients using statins prior to cancer diagnosis were 15% less likely to die from any cause or cancer specifically. Further investigation is needed to elaborate on their mode of action as well as their true significance on cancer prevention and perhaps as an adjuvant to cancer chemotherapy.

The stress-buffering effects of hope on adjustment to multiple sclerosis.

PubMed

Madan, Sindia; Pakenham, Kenneth I

2014-12-01

Hope is an important resource for coping with chronic illness; however, the role of hope in adjusting to multiple sclerosis (MS) has been neglected, and the mechanisms by which hope exerts beneficial impacts are not well understood. This study aims to examine the direct and stress-moderating effects of dispositional hope and its components (agency and pathways) on adjustment to MS. A total of 296 people with MS completed questionnaires at time 1 at 12 months later and time 2. Focal predictors were stress, hope, agency and pathways, and the adjustment outcomes were anxiety, depression, positive affect, positive states of mind and life satisfaction. Results of regression analyses showed that as predicted, greater hope was associated with better adjustment after controlling for the effects of time 1 adjustment and relevant demographics and illness variables. However, these direct effects of hope were subsumed by stress-buffering effects. Regarding the hope components, the beneficial impacts of agency emerged via a direct effects mechanism, whereas the effects of pathways were evidenced via a moderating mechanism. Findings highlight hope as an important protective coping resource for coping with MS and accentuate the roles of both agency and pathways thinking and their different modes of influence in this process.

Synchrony and exertion during dance independently raise pain threshold and encourage social bonding

PubMed Central

Tarr, Bronwyn; Launay, Jacques; Cohen, Emma; Dunbar, Robin

2015-01-01

Group dancing is a ubiquitous human activity that involves exertive synchronized movement to music. It is hypothesized to play a role in social bonding, potentially via the release of endorphins, which are analgesic and reward-inducing, and have been implicated in primate social bonding. We used a 2 × 2 experimental design to examine effects of exertion and synchrony on bonding. Both demonstrated significant independent positive effects on pain threshold (a proxy for endorphin activation) and in-group bonding. This suggests that dance which involves both exertive and synchronized movement may be an effective group bonding activity. PMID:26510676

Multiple myxoid cysts secondary to occupation.

PubMed

Connolly, M; de Berker, D A R

2006-05-01

We report the case of a 50-year-old woman who presented with eight digital myxoid cysts (DMCs) involving the fingers of both hands. They developed within 12 months of the patient starting a job that involved pushing a garment into an embroidery mould, thus exerting a downward force on the fingertips. The pressure exerted from this force could have potentially damaged the joint synovial capsule, leading to rupture and loss of synovial gel, thus inducing myxoid cysts. This case suggests that DMCs may be related to occupation, and to our knowledge, this is only the second reported case of occupationally induced DMCs.

Ozone and haze pollution effects on the contemporary land carbon cycle

NASA Astrophysics Data System (ADS)

Unger, N.

2016-12-01

Atmospheric pollutants have both beneficial and detrimental effects on carbon uptake by land ecosystems. Surface ozone damages leaf photosynthesis by oxidizing plant cells, while aerosols promote carbon uptake by increasing diffuse radiation and exert additional influences through concomitant perturbations to meteorology and hydrology. Here, I present new results from three assessment studies that employ Earth system modeling and multiple measurement datasets. First, we quantify the separate and combined effects of anthropogenic ozone and aerosol pollution on the global land carbon uptake. Second, we evaluate benefits to land ecosystem health from selective emission reductions in specific pollution sources and sectors. Finally, I show that the long-term climatic effects of mid-latitude air pollution boosts plant productivity in the Amazon by 10% on the annual average today.

The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases.

PubMed

Chiurchiù, Valerio; van der Stelt, Mario; Centonze, Diego; Maccarrone, Mauro

2018-01-01

Multiple sclerosis is the most common inflammatory demyelinating disease of the central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although the knowledge on its underlying neurobiological mechanisms has considerably improved, there is a still unmet need for new treatment options, especially for the progressive forms of the disease. Both preclinical and clinical data suggest that cannabinoids, derived from the Cannabis sativa plant, may be used to control symptoms such as spasticity and chronic pain, whereas only preclinical data indicate that these compounds and their endogenous counterparts, i.e. the endocannabinoids, may also exert neuroprotective effects and slow down disease progression. Here, we review the preclinical and clinical studies that could explain the therapeutic action of cannabinoid-based medicines, as well as the medical potential of modulating endocannabinoid signaling in multiple sclerosis, with a link to other neuroinflammatory disorders that share common hallmarks and pathogenetic features. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Experimente ueber den Einflusse von Metabolites und Antimetaboliten am Modell von Trichomonas Vaginalis. III. Mitteilung: Experimente mit Essentiellen Fettsaeuren (Experiments on the Influence of Metabolites and Antimetabolites on the Model of Trichomonas Vaginalis. III. Communication: Experiments with Essential Fatty Acids),

DTIC Science & Technology

The relationship between the double and trifold unsaturated fatty acids and Trichomonas vaginalis was tested. The experiments aimed at testing the...influence of vitamin F, linolic and linoleic acid upon multiplication of Trichomonas vaginalis . Vitamin F exerts trichomonacidal effect upon... Trichomonas vaginalis cultures. Linolic acid alone does not yet show great differences at concentrations of 0,01 to 0.05 mg/ml, as compared to the controls. At

Implications of the Babinet Principle for Casimir interactions

NASA Astrophysics Data System (ADS)

Maghrebi, Mohammad F.; Jaffe, Robert L.; Abravanel, Ronen

2011-09-01

We formulate the Babinet Principle (BP) as a relation between scattering amplitudes and combine it with multiple scattering techniques to derive new properties of electromagnetic Casimir forces. We show that the Casimir force exerted by a planar conductor or dielectric on a self-complementary perforated planar mirror is approximately half that on a uniform mirror independent of the distance between them. Also, the BP suggests that Casimir edge effects are generically anomalously small. Furthermore, the BP can be used to relate any planar object to its complementary geometry, a relation we use to estimate Casimir forces between two screens with apertures.

Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius

New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated inmore » Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.« less

The Tumor Microenvironment: A Pitch for Multiple Players

PubMed Central

Schiavoni, Giovanna; Gabriele, Lucia; Mattei, Fabrizio

2013-01-01

The cancer microenvironment may be conceptually regarded as a pitch where the main players are resident and non-resident cellular components, each covering a defined role and interconnected by a complex network of soluble mediators. The crosstalk between these cells and the tumor cells within this environment crucially determines the fate of tumor progression. Immune cells that infiltrate the tumor bed are transported there by blood circulation and exert a variety of effects, either counteracting or favoring tumor outgrowth. Here, we review and discuss the multiple populations composing the tumor bed, with special focus on immune cells subsets that positively or negatively dictate neoplastic progression. In this scenario, the contribution of cancer stem cells within the tumor microenvironment will also be discussed. Finally, we illustrate recent advances on new integrated approaches to investigate the tumor microenvironment in vitro. PMID:23616948

The Mediating Role of Self-Exertion on the Effects of Effort on Learning Virtues and Emotional Distress in Academic Failure in a Confucian Context

PubMed Central

Fwu, Bih-Jen; Chen, Shun-Wen; Wei, Chih-Fen; Wang, Hsiou-Huai

2017-01-01

Previous studies have found that in East Asian Confucian societies, hardworking students are often trapped in a dilemma of enjoying a positive moral image while suffering from emotional distress due to academic failure. This study intends to further explore whether the cultural-specific belief in self-exertion acts as a psychological mechanism to lessen these students’ negative emotions. A group of 288 college students in Taiwan were administered a questionnaire to record their responses to past academic failures. The results from structural equation modeling showed that self-exertion functioned as a mediator between the effects of effort on learning virtues and emotional distress. Self-exertion to fulfill one’s duty to oneself positively mediated the effect of effort on learning virtues, whereas self-exertion to fulfill one’s duty to one’s parents negatively mediated the effect of effort on emotional distress. Theoretical and cultural implications are further discussed. PMID:28119648

In muscle lengthening surgery multiple aponeurotomy does not improve intended acute effects and may counter-indicate: an assessment by finite element modelling.

PubMed

Yucesoy, Can A; Seref-Ferlengez, Zeynep; Huijing, Peter A

2013-01-01

The goal was to assess the effects of multiple aponeurotomy on mechanics of muscle with extramuscular myofascial connections. Using finite element modelling, effects of combinations of the intervention carried out at a proximal (P), an intermediate (I) and a distal (D) location were studied: (1) Case P, (2) Case P-I, (3) Case P-D and (4) Case P-I-D. Compared to Case P, the effects of multiple interventions on muscle geometry and sarcomere lengths were sizable for the distal population of muscle fibres: e.g. at high muscle length (1) summed gap lengths between the cut ends of aponeurosis increased by 16, 25 and 27% for Cases P-I, P-D and P-I-D, respectively, (2) characteristic substantial sarcomere shortening became more pronounced (mean shortening was 26, 29, 30 and 31% for Cases P, P-I, P-D and P-I-D, respectively) and (3) fibre stresses decreased (mean stress equalled 0.49, 0.39, 0.38 and 0.33 for Cases P, P-I, P-D and P-I-D, respectively). In contrast, no appreciable effects were shown for the proximal population. The overall change in sarcomere length heterogeneity was limited. Consequently, the effects of multiple aponeurotomy on muscle length-force characteristics were marginal: (1) a limited reduction in active muscle force (maximal 'muscle weakening effect' remained between 5 and 11%) and (2) an even less pronounced change in slack to optimum length range of force exertion (maximal 'muscle lengthening effect' distally was 0.2% for Case P-I-D) were shown. The intended effects of the intervention were dominated by the one intervention carried out closer to the tendon suggesting that aponeurotomies done additionally to that may counter-indicated.

Cotton photosynthetic regulation through nutrient and water availability

USDA-ARS?s Scientific Manuscript database

Photosynthesis is an extremely complicated process that is fundamental to supporting plant growth. It is regulated by multiple internal and external factors. Three factors regulating photosynthesis over which cotton producers can exert some influence are the levels of nitrogen, potassium, and soil...

Multiple anthropogenic stressors exert complex, interactive effects on a coral reef community

NASA Astrophysics Data System (ADS)

Muthukrishnan, Ranjan; Fong, Peggy

2014-12-01

Multiple natural and anthropogenic stressors impact coral reefs across the globe leading to declines of coral populations, but the relative importance of different stressors and the ways they interact remain poorly understood. Because coral reefs exist in environments commonly impacted by multiple stressors simultaneously, understanding their interactions is of particular importance. To evaluate the role of multiple stressors we experimentally manipulated three stressors (herbivore abundance, nutrient supply, and sediment loading) in plots on a natural reef in the Gulf of Panamá in the Eastern Tropical Pacific. Monitoring of the benthic community (coral, macroalgae, algal turf, and crustose coralline algae) showed complex responses with all three stressors impacting the community, but at different times, in different combinations, and with varying effects on different community members. Reduction of top-down control in combination with sediment addition had the strongest effect on the community, and led to approximately three times greater algal biomass. Coral cover was reduced in all experimental units with a negative effect of nutrients over time and a synergistic interaction between herbivore exclosures and sediment addition. In contrast, nutrient and sediment additions interacted antagonistically in their impacts on crustose coralline algae and turf algae so that in combination the treatments limited each other's effects. Interactions between stressors and temporal variability indicated that, while each stressor had the potential to impact community structure, their combinations and the broader environmental conditions under which they acted strongly influenced their specific effects. Thus, it is critical to evaluate the effects of stressors on community dynamics not only independently but also under different combinations or environmental conditions to understand how those effects will be played out in more realistic scenarios.

Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms.

PubMed

Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P; Sze, Siu Kwan

2016-05-18

Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases.

β-Cryptoxanthin is more bioavailable in humans from fermented orange juice than from orange juice.

PubMed

Hornero-Méndez, Dámaso; Cerrillo, Isabel; Ortega, Ángeles; Rodríguez-Griñolo, María-Rosario; Escudero-López, Blanca; Martín, Franz; Fernández-Pachón, María-Soledad

2018-10-01

Carotenoids, especially β-cryptoxanthin, exert multiple biological activities in the organism. Various processing techniques can improve carotenoid bioavailability in relation to the food matrix. The study objective was to compare the bioavailability of carotenoids from orange juice (OJ) with that from a beverage obtained by alcoholic fermentation of orange juice (FOB). Seven volunteers were recruited for a randomized, controlled, and crossover study. Post-intake plasma carotenoid concentrations were measured by HPLC in the subjects at 0-8 h after their consumption of OJ or FOB. β-Cryptoxanthin and lutein absorption was significantly higher from FOB than from OJ, but no significant difference in zeaxanthin absorption was found. The mean baseline-corrected area under the concentration curve (AUC 0-8 h ) for β-cryptoxanthin, lutein and zeaxanthin was 24.6-, 1.3- and 4.65-fold larger, respectively, after FOB versus OJ consumption. This fermented orange beverage could be an abundant source of bioavailable carotenoids, and its regular consumption may exert healthy effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Benefits of dietary fiber in clinical nutrition.

PubMed

Klosterbuer, Abby; Roughead, Zamzam Fariba; Slavin, Joanne

2011-10-01

Dietary fiber is widely recognized as an important part of a healthy diet and is a common addition to enteral nutrition (EN) formulas. Fiber sources differ in characteristics such as solubility, fermentability, and viscosity, and it is now well known that different types of fiber exert varying physiological effects in the body. Clinical studies suggest fiber can exert a wide range of benefits in areas such as bowel function, gut health, immunity, blood glucose control, and serum lipid levels. Although early clinical nutrition products contained fiber from a single source, it is now thought that blends of fiber from multiple sources more closely resemble a regular diet and may provide a greater range of benefits for the patient. Current recommendations support the use of dietary fiber in clinical nutrition when no contraindications exist, but little information exists about which types and combinations of fibers provide the relevant benefit in certain patient populations. This article summarizes the different types of fiber commonly added to EN products and reviews the current literature on the use of fiber blends in clinical nutrition.

Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms

PubMed Central

Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P.; Sze, Siu Kwan

2016-01-01

Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer’s health and risk of chronic diseases. PMID:27189269

Attenuation of Diabetes-induced Cardiac and Subcellular Defects by Sulphur-containing Amino Acids.

PubMed

Tappia, Paramjit S; Adameova, Adriana; Dhalla, Naranjan S

2018-01-30

Patients with diabetes mellitus have an increased risk of mortality due to cardiovascular complications. Supplementation with specific sulphur-containing amino acids is rapidly emerging as a possible therapeutic adjuvant for diabetes and associated cardiovascular complications. It is well-known that oxidative stress plays an important role in the pathogenesis of diabetes-induced cardiovascular disease, which is invariably associated with abnormal blood lipid profile, insulin resistance and other symptoms of metabolic syndrome. Cysteine and taurine are among the most common sulphur-containing amino acids and their cellular levels decline during diabetes that may contribute to the development of the cardiomyopathy. Although sulphur-containing agents exert multiple actions on cellular and subcellular functions in the heart, they also exhibit antioxidant properties and thus may exert beneficial effects in different pathophysiological conditions. It is concluded that reduction of oxidative stress by cysteine and taurine may serve as an important mechanism for the attenuation of diabetes-induced subcellular and functional abnormalities in the heart. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Do placebo expectations influence perceived exertion during physical exercise?

PubMed

Mothes, Hendrik; Leukel, Christian; Seelig, Harald; Fuchs, Reinhard

2017-01-01

This study investigates the role of placebo expectations in individuals' perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a) the effects of exercise and b) the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE) measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting "scientific evidence" that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment) would additionally enhance exercise benefits or would only be worn for control purposes. Participants' physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels) in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion.

Do placebo expectations influence perceived exertion during physical exercise?

PubMed Central

Leukel, Christian; Seelig, Harald; Fuchs, Reinhard

2017-01-01

This study investigates the role of placebo expectations in individuals’ perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a) the effects of exercise and b) the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE) measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting “scientific evidence” that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment) would additionally enhance exercise benefits or would only be worn for control purposes. Participants’ physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels) in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion. PMID:28662168

Towards Reconciliation of Several Dualities in Physician Leadership

PubMed Central

Walker, Keith; Kraines, Gerry

2015-01-01

Leadership has a renewed focus in healthcare, and physicians are being increasingly involved in a range of leadership roles. The aim of this paper is to discuss several dualities that exert tensions at the systems and individual levels. Although oppositional, the common dualities of physician leadership are not mutually exclusive but represent a complex, dynamic and interdependent relationship, often coexisting with each other and exerting tensions in multiple dimensions. The authors contend that a dialectic understanding – instead of either/or or finding a middle ground – of the opposite poles of these dualities allows for generating meaningful leadership perspectives and choices. PMID:25947031

Simultaneous Retrieval of Multiple Aerosol Parameters Using a Multi-Angular Approach

NASA Technical Reports Server (NTRS)

Kuo, K. S.; Weger, R. C.; Welch, R. M.

1997-01-01

Atmospheric aerosol particles, both natural and anthropogenic, are important to the earth's radiative balance through their direct and indirect effects. They scatter the incoming solar radiation (direct effect) and modify the shortwave reflective properties of clouds by acting as cloud condensation nuclei (indirect effect). Although it has been suggested that aerosols exert a net cooling influence on climate, this effect has received less attention than the radiative forcing due to clouds and greenhouse gases. In order to understand the role that aerosols play in a changing climate, detailed and accurate observations are a prerequisite. The retrieval of aerosol optical properties by satellite remote sensing has proven to be a difficult task. The difficulty results mainly from the tenuous nature and variable composition of aerosols. To date, with single-angle satellite observations, we can only retrieve reliably against dark backgrounds, such as over oceans and dense vegetation. Even then, assumptions must be made concerning the chemical composition of aerosols. The best hope we have for aerosol retrievals over bright backgrounds are observations from multiple angles, such as those provided by the MISR and POLDER instruments. In this investigation we examine the feasibility of simultaneous retrieval of multiple aerosol optical parameters using reflectances from a typical set of twelve angles observed by the French POLDER instrument. The retrieved aerosol optical parameters consist of asymmetry factor, single scattering albedo, surface albedo, and optical thickness.

Common carp disrupt ecosystem structure and function through middle-out effects

USGS Publications Warehouse

Kaemingk, Mark A.; Jolley, Jeffrey C.; Paukert, Craig P.; Willis, David W.; Henderson, Kjetil R.; Holland, Richard S.; Wanner, Greg A.; Lindvall, Mark L.

2016-01-01

Middle-out effects or a combination of top-down and bottom-up processes create many theoretical and empirical challenges in the realm of trophic ecology. We propose using specific autecology or species trait (i.e. behavioural) information to help explain and understand trophic dynamics that may involve complicated and non-unidirectional trophic interactions. The common carp (Cyprinus carpio) served as our model species for whole-lake observational and experimental studies; four trophic levels were measured to assess common carp-mediated middle-out effects across multiple lakes. We hypothesised that common carp could influence aquatic ecosystems through multiple pathways (i.e. abiotic and biotic foraging, early life feeding, nutrient). Both studies revealed most trophic levels were affected by common carp, highlighting strong middle-out effects likely caused by common carp foraging activities and abiotic influence (i.e. sediment resuspension). The loss of water transparency, submersed vegetation and a shift in zooplankton dynamics were the strongest effects. Trophic levels furthest from direct pathway effects were also affected (fish life history traits). The present study demonstrates that common carp can exert substantial effects on ecosystem structure and function. Species capable of middle-out effects can greatly modify communities through a variety of available pathways and are not confined to traditional top-down or bottom-up processes.

Analysis of genotoxic activity of ketamine and rocuronium bromide using the somatic mutation and recombination test in Drosophila melanogaster.

PubMed

Koksal, Pakize Muge; Gürbüzel, Mehmet

2015-03-01

The present study evaluated the mutagenic and recombinogenic effects of two commonly used anesthetic agents, ketamine and rocuronium bromide, in medicine using the wing somatic mutation and recombination test (SMART) in Drosophila. The standard (ST) cross and the high-bioactivation (HB) cross with high sensitivity to procarcinogens and promutagens were used. The SMART test is based on the loss of heterozygosity, which occurs via various mechanisms, such as chromosome loss and deletion, half-translocation, mitotic recombination, mutation, and non-disjunction. Genetic alterations occurring in the somatic cells of the wing's imaginal discs result in mutant clones in the wing blade. Three-day-old trans-heterozygous larvae with two recessive markers, multiple wing hairs (mwh) and flare (flr(3)), were treated with ketamine and rocuronium bromide. Analysis of the ST cross indicated that ketamine exhibited genotoxicity activity and that this activity was particularly dependent on homologous mitotic recombination at concentrations of 250 μg/ml and above. Rocuronium bromide did not exert mutagenic and/or recombinogenic effects. In the HB cross, ketamine at a concentration of 1000 μg/ml and rocuronium bromide at all concentrations, with the exception of 250 μg/ml (inconclusive), exerted genotoxic effects, which could also be associated with the increase in mitotic recombination. Copyright © 2015 Elsevier B.V. All rights reserved.

Triptolide prevents extracellular matrix accumulation in experimental diabetic kidney disease by targeting microRNA-137/Notch1 pathway.

PubMed

Han, Fei; Wang, Shanshan; Chang, Yunpeng; Li, Chunjun; Yang, Juhong; Han, Zhe; Chang, Baocheng; Sun, Bei; Chen, Liming

2018-03-01

MicroRNAs (miRNAs) are involved in multiple biological functions via suppressing target genes. Triptolide is a monomeric compound isolated from a traditional Chinese herb, which exerts protective roles in many kinds of glomerular diseases. However, our understanding of the triptolide effect on miRNAome is still limited. In this study, we found that triptolide significantly decreased albuminuria and improved glomerulosclerosis in rats with diabetic kidney disease (DKD). And triptolide also inhibited extracellular matrix (ECM) protein accumulation and the notch1 pathway activation under diabetic conditions. MiR-137 was significantly decreased in the HG (high glucose)-treated HRMCs and in the kidney tissues of the diabetic rats, but was upregulated by triptolide. In addition, overexpression of miR-137 exerted similar effects to those of triptolide, while miR-137 inhibition aggravated ECM protein accumulation. Luciferase reporter assay results demonstrated that miR-137 directly targets Notch1. Furthermore, the miR-137-dependent effects were due to Notch1 suppression that in turn inhibited ECM protein expression, key mediators of glomerulosclerosis. Finally, downregulation of miR-137 reversed the ECM inhibition role of triptolide in HG cultured HRMCs. Taken together, these findings indicate that triptolide is a potential therapeutic option for DKD and that miR-137/Notch1 pathway play roles in the anti-glomerulosclerosis mechanism of triptolide. © 2017 Wiley Periodicals, Inc.

Cell-based Therapy for Acute Organ Injury: Preclinical Evidence and On-going Clinical Trials Using Mesenchymal Stem Cells

PubMed Central

Monsel, Antoine; Zhu, Ying-gang; Gennai, Stephane; Hao, Qi; Liu, Jia; Lee, Jae W.

2014-01-01

Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver or brain. Genomic, proteomic and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of pro-mitotic, anti-apoptotic, anti-inflammatory and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, we review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. PMID:25211170

Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

PubMed

Canitano, Andrea; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Federici, Cristina; Fais, Stefano

2016-07-01

Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chlorine dioxide-induced and Congo red-inhibited Marangoni effect on the chlorite-trithionate reaction front

NASA Astrophysics Data System (ADS)

Liu, Yang; Ren, Xingfeng; Pan, Changwei; Zheng, Ting; Yuan, Ling; Zheng, Juhua; Gao, Qingyu

2017-10-01

Hydrodynamic flows can exert multiple effects on an exothermal autocatalytic reaction, such as buoyancy and the Marangoni convection, which can change the structure and velocity of chemical waves. Here we report that in the chlorite-trithionate reaction, the production and consumption of chlorine dioxide can induce and inhibit Marangoni flow, respectively, leading to different chemo-hydrodynamic patterns. The horizontal propagation of a reaction-diffusion-convection front was investigated with the upper surface open to the air. The Marangoni convection, induced by gaseous chlorine dioxide on the surface, produced from chlorite disproportionation after the proton autocatalysis, has the same effect as the heat convection. When the Marangoni effect is removed by the reaction of chlorine dioxide with the Congo red (CR) indicator, an oscillatory propagation of the front tip is observed under suitable conditions. Replacing CR with bromophenol blue (BPB) distinctly enhanced the floating, resulting in multiple vortexes, owing to the coexistence between BPB and chlorine dioxide. Using the incompressible Navier-Stokes equations coupled with reaction-diffusion and heat conduction equations, we numerically obtain various experimental scenarios of front instability for the exothermic autocatalytic reaction coupled with buoyancy-driven convection and Marangoni convection.

Long Noncoding RNAs: a New Regulatory Code in Metabolic Control

PubMed Central

Zhao, Xu-Yun; Lin, Jiandie D.

2015-01-01

Long noncoding RNAs (lncRNAs) are emerging as an integral part of the regulatory information encoded in the genome. LncRNAs possess the unique capability to interact with nucleic acids and proteins and exert discrete effects on numerous biological processes. Recent studies have delineated multiple lncRNA pathways that control metabolic tissue development and function. The expansion of the regulatory code that links nutrient and hormonal signals to tissue metabolism gives new insights into the genetic and pathogenic mechanisms underlying metabolic disease. This review discusses lncRNA biology with a focus on its role in the development, signaling, and function of key metabolic tissues. PMID:26410599

Interventions for Tobacco Smoking

PubMed Central

Schlam, Tanya R.; Baker, Timothy B.

2017-01-01

Around 19% of U.S. adults smoke cigarettes, and smoking remains the leading avoidable cause of death in this country. Without treatment only ~5% of smokers who try to quit achieve long-term abstinence, but evidence-based cessation treatment increases this figure to 10-30%. The process of smoking cessation comprises different pragmatically defined phases, and these can help guide smoking treatment development and evaluation. This review evaluates the effectiveness of smoking interventions for smokers who are unwilling to make a quit attempt (Motivation Phase), who are willing to make a quit attempt (Cessation Phase), who have recently quit (Maintenance Phase), and who have recently relapsed (Relapse Recovery Phase). Multiple effective treatments exist for some phases (Cessation), but not others (Relapse Recovery). A chronic care approach to treating smoking requires effective interventions for every phase, especially interventions that exert complementary effects both within and across phases, and that can be disseminated broadly and cost-effectively. PMID:23297788

[Visits of patients with exertional rhabdomyolysis to the Emergency Department at Landspítali, The National University Hospital of Iceland in the years 2008-2012].

PubMed

Halldorsson, Arnljotur Bjorn; Benedikz, Elisabet; Olafsson, Isleifur; Mogensen, Brynjolfur

2016-03-01

Overexertion and too much training are among the -multiple etiologies of rhabdomyolysis. Creatine kinase (CK) and myo-globine, released from skeletal muscle cells, are useful for diagnosis and follow-up. Acute kidney injury is a serious complication of myoglobinemia. Literature on exertional rhabdomyolysis in the general population is scarce. The aim of this study was to investigate the epidemiology of exertional rhabdomyolysis among patients diagnosed at Landspítali The National University Hospital of Iceland in 2008-2012. The study was retrospective and observational. All patients presenting with muscle pain after exertion and elevated creatine kinase >1000 IU/L, during the period from 1 January 2008 to 31 December 2012, were included. Patients with CK elevations secondary to causes other than exertion were excluded. Variables included: patient number and gender, CK-levels, date of hospital admission, cause of rhabdomyolysis, location of injured muscle groups, length of hospital stay, complications and means of fluid replacement. Population figures of the capital region were gathered from Statistics Iceland and information on sport practice in the capital region from The National Olympic and Sports Association of Iceland. Exertional rhabdomyolysis was diagnosed in 54 patients, 18 females (33,3%) and 36 males (66,7%), or 8,3% of rhabdomyolysis cases from all causes in the study period (648 cases). Incidence in the capital region was 5,0/100.000 inhabitants per year in the study period. Median age was 28 years and median CK-level was 24.132 IU/L. CK-levels were higher among females but the difference between genders was not significant. Muscle groups of the upper and lower extremities were most frequently affected (89%). Thirty patients received intravenous fluids. They had significantly higher CK values than other patients. One patient developed acute kidney injury. Information on sport practice and physical training in the capital region was not available. Exertional rhabdomyolysis is uncommon but mostly affects younger people. Information on the practice of exertion among males and females is not available but CK-levels were not significantly different between genders, age groups or different muscle groups. CK-levels were high but complications uncommon. Studies of exertional rhabdomyolysis in the general population are lacking. Rhabdomyolysis, exertion, sports, physical training, CK elevation. Correspondence: Brynjolfur Mogensen, brynmog@landspitali.is.

Lithium lengthens circadian period of cultured brain slices in area specific manner.

PubMed

Yoshikawa, Tomoko; Honma, Sato

2016-11-01

Lithium has been used for the treatment of bipolar disorder (BD). However, the mechanisms how lithium exerts its mood stabilizing effects remain to be studied. The disorder in circadian pacemaking has been suggested as an underlying mechanism of the characteristic mood instability of the BD. Lithium is also known to lengthen the circadian periods. We recently proposed that chronic methamphetamine treatment induced circadian oscillation as a complex oscillator including multiple dopaminergic brain areas, and the complex oscillator regulates behavior rhythm independent from the central circadian oscillator in the suprachiasmatic nucleus (SCN). Sleep-wake pattern of rapid cycling BD exhibits similar rhythm disorganization to methamphetamine treated animals. Therefore, we hypothesized that the dysregulated circadian rhythm in BD patients is caused by desynchronization of sleep-wake rhythms from the central clock in the SCN, and that mood stabilizing effect of lithium is achieved through their resynchronization. In the present experiment, we examined how lithium affects the circadian rhythms of brain areas involved in the complex oscillator as well as the SCN. Here we report that lithium lengthens the circadian periods in the SCN, olfactory bulb, median eminence and substantia nigra with dose and area specific manner. The effective lithium dose was much higher than the plasma levels that are required for lengthening the circadian behavior rhythms as well for therapeutic use. Low dose of lithium did not lengthen the period but enhanced the amplitude of circadian rhythms, which may exert therapeutic effects on BD. Copyright © 2016 Elsevier B.V. All rights reserved.

MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Shun; Huang, Haijiao; Li, Nanhong

2016-05-13

MicroRNAs are a large class of tiny noncoding RNAs, which have emerged as critical regulators of gene expression, and thus are involved in multiple cellular processes, including cellular senescence. MicroRNA-33 has previously been established to exert crucial effect on cell proliferation, lipid metabolism and cholesterol metabolism. Nonetheless, the association between microRNA-33 and cellular senescence and its underlying molecular mechanism are far to be elucidated. The present study has attempted to probe into the effect of microRNA-33 on MEFs senescence. Our data unveiled that microRNA-33 was dramatically down-regulated in senescent MEFs compared to the young MEFs, and ectopic expression of microRNA-33more » promoted MEFs senescence, while knock-down of microRNA-33 exhibited a protective effect against senescence phenotype. Moreover, we verified CDK6 as a direct target of microRNA-33 in mouse. Silencing of CDK6 induced the premature senescence phenotype of MEFs similarly as microRNA-33, while enforced expression of CDK6 significantly reverse the senescence-induction effect of microRNA-33. Taken together, our results suggested that microRNA-33 enhanced the replicative senescence of MEFs potentially by suppressing CDK6 expression. -- Highlights: •MicroRNA-33 was dramatically down-regulated in senescent MEF cells. •Altered expression of microRNA-33 exerted a critical role in MEFs senescence. •MicroRNA-33 promoted the replicative senescence of MEFs via targeting of CDK6.« less

Effects of prior physical exertion on tolerance to hypoxia, orthostatic stress, and physical fatigue.

DOT National Transportation Integrated Search

1982-03-01

Ten healthy men, 20-35 years old, were tested for tolerance to hypoxia, orthostatic stress, and physical fatigue after a period of rest, and, on another occasion, after a period of physical exertion. Exertion consisted of four 10-min periods of pedal...

Interacting Compasses

ERIC Educational Resources Information Center

Riveros, Hector G.; Betancourt, Julian

2009-01-01

The use of multiple compasses to map and visualize magnetic fields is well-known. The magnetic field exerts a torque on the compasses aligning them along the lines of force. Some science museums show the field of a magnet using a table with many compasses in a closely packed arrangement. However, the very interesting interactions that occur…

Melatonin as a multifunctional anti-cancer molecule: Implications in gastric cancer.

PubMed

Asghari, Mohammad Hossein; Moloudizargari, Milad; Ghobadi, Emad; Fallah, Marjan; Abdollahi, Mohammad

2017-09-15

Gastric cancer (GC) is a predominant malignancy with a high mortality rate affecting a large population worldwide. The etiology of GC is multifactorial spanning from various genetic determinants to different environmental causes. Current tretaments of GC are not efficient enough and require improvements to minimize the adverse effects. Melatonin, a naturally occurring compound with known potent inhibitory effects on cancer cells is one of the major candidates which can be recruited herein. Here we reviewed the articles conducted on the therapeutic effects of melatonin in gastric cancer in various models. The results are classified according to different aspects of cancer pathogenesis and the molecular mechanisms by which melatonin exerts its effects. Melatonin could be used to combat GC exploiting its effects on multiple aspects of its pathogenesis, including formation of cancer cells, tumor growth and angiogenesis, differentiation and metastasis as well as enhancing the anti-tumor immunity. Melatonin is a pleiotropic anti-cancer molecule that affects malignant cells via multiple mechanisms. It has been shown to benefit cancer patients indirectly by reducing side effects of current therapies which have been discussed in this review. This field of research is still underdeveloped and may serve as an interesting subject for further studies aiming at the molecular mechanisms of melatonin and novel treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Something's got to give: the effects of dual-goal difficulty, goal progress, and expectancies on resource allocation.

PubMed

Schmidt, Aaron M; Dolis, Chad M

2009-05-01

The current study developed and tested a model of the interplay among goal difficulty, goal progress, and expectancy over time in influencing resource allocation toward competing demands. The results provided broad support for the theoretical model. As predicted, dual-goal expectancy-the perceived likelihood of meeting both goals in competition-played a central role, moderating the relationship between relative goal progress and resource allocation. Dual-goal difficulty was also found to exert an important influence on multiple-goal self-regulation. Although it did not influence total productivity across both tasks combined, it did combine with other model components to influence the relative emphasis of one task over another. These results suggest that the cumulative demands placed by multiple difficult goals may exceed individuals' perceived capabilities and may lead to partial or total abandonment of 1 goal to ensure attainment of the other. The model helps shed light on some of the conflicting theoretical propositions and empirical results obtained in prior work. Implications for theory and research regarding multiple-goal self-regulation are discussed. (c) 2009 APA, all rights reserved.

Physiological and psychological fatigue in extreme conditions: the military example.

PubMed

Weeks, Sharon R; McAuliffe, Caitlin L; Durussel, David; Pasquina, Paul F

2010-05-01

The extreme conditions causing fatigue in military service members in combat and combat training deserve special consideration. The collective effects of severe exertion, limited caloric intake, and sleep deprivation, combined with the inherent stressors of combat, lead to both physiological and psychological fatigue that may significantly impair performance. Studies of combat training have revealed a myriad of endocrine, cognitive, and neurological changes that occur as a result of exposure to extreme conditions. Further contributory effects of multiple military deployments, post-traumatic stress disorder, and traumatic brain injury may also influence both the susceptibility to and expression of fatigue states. Further research is needed to explore these effects to enhance military readiness and performance as well as prevent injuries. Copyright (c) 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Basolateral amygdalar D2 receptor activation is required for the companions-exerted suppressive effect on the cocaine conditioning.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Yu, Lung; Wang, Ching-Yi

2017-01-01

The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Three cage mates, serving as companions, were arranged to house with the experimental mice in the cocaine conditioning compartment throughout the cocaine conditioning sessions. Approximately 1week before the conditioning procedure, intracranial ibotenic acid infusions were done in an attempt to cause excitotoxic lesions targeting bilateral BLA, DH and DLS. Albeit their BLA, DH, and DLS lesions, the lesioned mice exhibited comparable cocaine-induced CPP magnitudes compared to the intact and sham lesion controls. Bilateral BLA, but not DH or DLS, lesions abolished the companions-exerted suppressive effect on the cocaine-induced CPP. Intact mice receiving intra-BLA infusion of raclopride, a selective D2 antagonist, 30min prior to the cocaine conditioning did not exhibit the companions-exerted suppressive effect on the cocaine-induced CPP. Intra-BLA infusion of Sch23390, a selective D1 antagonist, did not affect the companions-exerted suppressive effect on the CPP. These results, taken together, prompt us to conclude that the intactness of BLA is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Importantly, activation of D2 receptor in the BLA is required for such suppressive effect on the CPP. Copyright © 2016 Elsevier Inc. All rights reserved.

Job characteristics in relation to the prevalence of myocardial infarction in the US Health Examination Survey (HES) and the Health and Nutrition Examination Survey (HANES).

PubMed

Karasek, R A; Theorell, T; Schwartz, J E; Schnall, P L; Pieper, C F; Michela, J L

1988-08-01

Associations between psychosocial job characteristics and past myocardial infarction (MI) prevalence for employed males were tested with the Health Examination Survey (HES) 1960-61, N = 2,409, and the Health and Nutrition Examination Survey (HANES) 1971-75, N = 2,424. A new estimation method is used which imputes to census occupation codes, job characteristic information from national surveys of job characteristics (US Department of Labor, Quality of Employment Surveys). Controlling for age, we find that employed males with jobs which are simultaneously low in decision latitude and high in psychological work load (a multiplicative product term isolating 20 per cent of the population) have a higher prevalence of myocardial infarction in both data bases. In a logistic regression analysis, using job measures adjusted for demographic factors and controlling for age, race, education, systolic blood pressure, serum cholesterol, smoking (HANES only), and physical exertion, we find a low decision latitude/high psychological demand multiplicative product term associated with MI in both data bases. Additional multiple logistic regressions show that low decision latitude is associated with increased prevalence of MI in both the HES and the HANES. Psychological workload and physical exertion are significant only in the HANES.

Job characteristics in relation to the prevalence of myocardial infarction in the US Health Examination Survey (HES) and the Health and Nutrition Examination Survey (HANES).

PubMed Central

Karasek, R A; Theorell, T; Schwartz, J E; Schnall, P L; Pieper, C F; Michela, J L

1988-01-01

Associations between psychosocial job characteristics and past myocardial infarction (MI) prevalence for employed males were tested with the Health Examination Survey (HES) 1960-61, N = 2,409, and the Health and Nutrition Examination Survey (HANES) 1971-75, N = 2,424. A new estimation method is used which imputes to census occupation codes, job characteristic information from national surveys of job characteristics (US Department of Labor, Quality of Employment Surveys). Controlling for age, we find that employed males with jobs which are simultaneously low in decision latitude and high in psychological work load (a multiplicative product term isolating 20 per cent of the population) have a higher prevalence of myocardial infarction in both data bases. In a logistic regression analysis, using job measures adjusted for demographic factors and controlling for age, race, education, systolic blood pressure, serum cholesterol, smoking (HANES only), and physical exertion, we find a low decision latitude/high psychological demand multiplicative product term associated with MI in both data bases. Additional multiple logistic regressions show that low decision latitude is associated with increased prevalence of MI in both the HES and the HANES. Psychological workload and physical exertion are significant only in the HANES. PMID:3389427

Workplace and individual risk factors for carpal tunnel syndrome.

PubMed

Burt, Susan; Crombie, Ken; Jin, Yan; Wurzelbacher, Steve; Ramsey, Jessica; Deddens, James

2011-12-01

To quantify the relationship between workplace physical factors, particularly hand activity level (HAL) and forceful exertion and carpal tunnel syndrome (CTS), while taking into account individual factors. To compare quantitative exposure assessment measures with more practical ratings-based measures. In a group of healthcare and manufacturing workers, each study participant's job tasks were evaluated for HAL, forceful exertion and other physical stressors and videotaped for further analysis, including frequency and duration of exertion and postural deviation. Electrodiagnostic testing of median and ulnar nerves and questionnaires were administered to all participants. A CTS case required median mononeuropathy and symptoms on hand diagrams in fingers 1-3. Multiple logistic regression models were used to analyse associations between job and individual factors and CTS. Of 477 workers studied, 57 (11.9%) were dominant hand CTS cases. Peak force ≥70% maximum voluntary contraction versus <20% maximum voluntary contraction resulted in an OR of 2.74 (1.32-5.68) for CTS. Among those with a body mass index ≥30, the OR for ≥15 exertions per minute was 3.35 (1.14-9.87). Peak worker ratings of perceived exertion increased the odds for CTS by 1.14 (1.01-1.29) for each unit increase on the 10-point scale. The odds for CTS increased by 1.38 (1.05-1.81) for each unit increase on the HAL 10-point scale among men, but not women. Combined force and HAL values above the ACGIH TLV for HAL resulted in an OR of 2.96 (1.51-5.80) for CTS. Quantitative and ratings-based job exposure measures were each associated with CTS. Obesity increased the association between frequency of exertion and CTS.

Exercise-associated Excessive Dynamic Airway Collapse in Military Personnel.

PubMed

Weinstein, Daniel J; Hull, James E; Ritchie, Brittany L; Hayes, Jackie A; Morris, Michael J

2016-09-01

Evaluation of military personnel for exertional dyspnea can present a diagnostic challenge, given multiple unique factors that include wide variation in military deployment. Initial consideration is given to common disorders such as asthma, exercise-induced bronchospasm, and inducible laryngeal obstruction. Excessive dynamic airway collapse has not been reported previously as a cause of dyspnea in these individuals. To describe the clinical and imaging characteristics of military personnel with exertional dyspnea who were found to have excessive dynamic collapse of large airways during exercise. After deployment to Afghanistan or Iraq, 240 active U.S. military personnel underwent a standardized evaluation to determine the etiology of persistent dyspnea on exertion. Study procedures included full pulmonary function testing, impulse oscillometry, exhaled nitric oxide measurement, methacholine challenge testing, exercise laryngoscopy, cardiopulmonary exercise testing, and fiberoptic bronchoscopy. Imaging included high-resolution computed tomography with inspiratory and expiratory views. Selected individuals underwent further imaging with dynamic computed tomography. A total of five men and one woman were identified as having exercise-associated excessive dynamic airway collapse on the basis of the following criteria: (1) exertional dyspnea without resting symptoms, (2) focal expiratory wheezing during exercise, (3) functional collapse of the large airways during bronchoscopy, (4) expiratory computed tomographic imaging showing narrowing of a large airway, and (5) absence of underlying apparent pathology in small airways or pulmonary parenchyma. Identification of focal expiratory wheezing correlated with bronchoscopic and imaging findings. Among 240 military personnel evaluated after presenting with postdeployment exertional dyspnea, a combination of symptoms, auscultatory findings, imaging, and visualization of the airways by bronchoscopy identified six individuals with excessive dynamic central airway collapse as the sole apparent cause of dyspnea. Exercise-associated excessive dynamic airway collapse should be considered in the differential diagnosis of exertional dyspnea.

The effect of grip force, stroke rotation and frequency on discomfort for a torqueing tasks.

PubMed

Bano, Farheen; Mallick, Zulqernian; Khan, Abid Ali

2015-08-08

Occupational tasks involve awkward upper limb postures, especially movement of forearm with repetitive combined gripping and torqueing exertions, which may lead to development of WMSDs. From the literature survey it was observed that there was a lack of studies focussed on the combined effect of torque and grip exertions on forearm discomfort. The present study was to investigate the effects of grip force, stroke rotation and frequency of exertions on discomfort and Electromyography (EMG) activities of the forearm muscles in a repetitive torqueing task. Twenty-seven male participants volunteered in this study. The participants performed repetitive exertions for a 5 minutes duration for each combination of the different levels of stroke rotation, grip force and frequency of exertions. Three levels of stroke rotation, three levels of grip force and three levels of frequency of exertion were chosen as independent variables. Therefore a 3 × 3 customized factorial design was used for the experiment for each level of grip force. Hence, the study was divided into three groups on the basis of grip force (50N, 70N and 90N). The ANOVA showed that stroke rotation and frequency of exertion were significant on discomfort. Further Students Newmann test (SNK) revealed that discomfort was increased with increasing stroke rotation and frequency of exertion. The multivariate analysis of variances (MANOVA) performed on EMG data instead of ANOVA because EMG activities of five muscles simultaneously were recorded. The Results found that extensor muscles were more fatigued in torqueing with gripping task. It was found that stroke rotation for the torqueing tasks must be kept below 45°. It was concluded that it is important to control stroke rotation to improve performance of repetitive torqueing activity.

Bioactive Compounds from Macroalgae in the New Millennium: Implications for Neurodegenerative Diseases

PubMed Central

Barbosa, Mariana; Valentão, Patrícia; Andrade, Paula B.

2014-01-01

Marine environment has proven to be a rich source of structurally diverse and complex compounds exhibiting numerous interesting biological effects. Macroalgae are currently being explored as novel and sustainable sources of bioactive compounds for both pharmaceutical and nutraceutical applications. Given the increasing prevalence of different forms of dementia, researchers have been focusing their attention on the discovery and development of new compounds from macroalgae for potential application in neuroprotection. Neuroprotection involves multiple and complex mechanisms, which are deeply related. Therefore, compounds exerting neuroprotective effects through different pathways could present viable approaches in the management of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. In fact, several studies had already provided promising insights into the neuroprotective effects of a series of compounds isolated from different macroalgae species. This review will focus on compounds from macroalgae that exhibit neuroprotective effects and their potential application to treat and/or prevent neurodegenerative diseases. PMID:25257784

Bioactive compounds from macroalgae in the new millennium: implications for neurodegenerative diseases.

PubMed

Barbosa, Mariana; Valentão, Patrícia; Andrade, Paula B

2014-09-25

Marine environment has proven to be a rich source of structurally diverse and complex compounds exhibiting numerous interesting biological effects. Macroalgae are currently being explored as novel and sustainable sources of bioactive compounds for both pharmaceutical and nutraceutical applications. Given the increasing prevalence of different forms of dementia, researchers have been focusing their attention on the discovery and development of new compounds from macroalgae for potential application in neuroprotection. Neuroprotection involves multiple and complex mechanisms, which are deeply related. Therefore, compounds exerting neuroprotective effects through different pathways could present viable approaches in the management of neurodegenerative diseases, such as Alzheimer's and Parkinson's. In fact, several studies had already provided promising insights into the neuroprotective effects of a series of compounds isolated from different macroalgae species. This review will focus on compounds from macroalgae that exhibit neuroprotective effects and their potential application to treat and/or prevent neurodegenerative diseases.

Evaluation of sublethal effects of polymer-based essential oils nanoformulation on the german cockroach.

PubMed

González, Jorge Werdin; Yeguerman, Cristhian; Marcovecchio, Diego; Delrieux, Claudio; Ferrero, Adriana; Band, Beatriz Fernández

2016-08-01

The German cockroach, Blattella germanica (L.), is a serious household and public health pest worldwide. The aim of the present study was to evaluate the sublethal activity of polymer-based essential oils (EOs) nanoparticles (NPs) on adults of B. germanica. The LC50 and LC25 for contact toxicity were determined. To evaluate the repellency of EOs and NPs at LC25, a software was specially created in order to track multiple insects on just-recorded videos, and generate statistics using the obtained information. The effects of EOs and NPs at LC25 and LC50 on the nutritional physiology were also evaluated. The results showed that NPs exerted sublethal effects on the German cockroach, since these products enhance the repellent effects of the EOs and negatively affected the nutritional indices and the feeding deterrence index. Copyright © 2016 Elsevier Inc. All rights reserved.

Maternal effects on offspring depend on female mating pattern and offspring environment in yellow dung flies.

PubMed

Tregenza, Tom; Wedell, Nina; Hosken, David J; Ward, Paul I

2003-02-01

Direct costs and benefits to females of multiple mating have been shown to have large effects on female fecundity and longevity in several species. However, with the exception of studies examining genetic benefits of polyandry, little attention has been paid to the possible effects on offspring of multiple mating by females. We propose that nongenetic effects of maternal matings on offspring fitness are best viewed in the same context as other maternal phenotype effects on offspring that are well known even in species lacking parental care. Hence, matings can exert effects on offspring in the same way as other maternal environment variables, and are likely to interact with such effects. We have conducted a study using yellow dung flies (Scathophaga stercoraria), in which we independently manipulated female mating rate, number of mates and maternal thermal environment and measured subsequent fecundity, hatching success, and offspring life-history traits. To distinguish between direct effects of matings and potential genetic benefits of polyandry we split broods and reared offspring at three different temperature regimes. This allowed us to demonstrate that although we could not detect any simple benefits or costs to matings, there are effects of maternal environment on offspring and these effects interact with female mating regime affecting offspring fitness. Such interactions between female phenotype and the costs and benefits of matings have potentially broad implications for understanding female behavior.

MicroRNA-320 involves in the cardioprotective effect of insulin against myocardial ischemia by targeting survivin.

PubMed

Yang, Ni; Wu, Liuzhong; Zhao, Ying; Zou, Ning; Liu, Chunfeng

2018-04-01

It is generally accepted that insulin exerts an antiapoptotic effect against ischemia/reperfusion through the activation of PI3K/Akt/mTOR pathway. MicroRNAs involve in multiple cardiac pathophysiological processes, including ischemia/reperfusion-induced cardiac injury. However, the regulation of microRNAs in the cardioprotective effect of insulin is rarely discussed. In this study, using a cell model of ischemia through culturing H9C2 cardiac myocytes in serum-free medium with hypoxia, we demonstrated that pretreatment with insulin significantly inhibited cell apoptosis and downregulated microRNA-320 (miR-320) expression. Interestingly, miR-320 mimic impaired the cardioprotective effect of insulin against myocardial ischemia injury by targeting survivin, which is a member of the family of inhibitor of apoptosis proteins. Suppression miR-320 expression by miR-320 inhibitor in H9C2 cells with myocardial ischemia mimics the cardioprotective effect of insulin by maintaining survivin expression. Taken together, miR-320-mediated survivin expression involves in cardioprotective effect of insulin against myocardial ischemia injury. Myocardial ischemia/reperfusion (I/R) injury remains an important clinical problem with extremely deficient clinical therapies. Insulin exerts an antiapoptotic effect against I/R through the activation of PI3K/Akt/mTOR pathway. Here, we provided evidences to show that microRNA-320 involves in the cardioprotective effect of insulin by targeting survivin, which is an inhibitor of apoptosis protein and functions as a key regulator in cell apoptosis and involves in the tumour genesis and progression. Our findings may provide a new potential therapeutic strategy for I/R injury and ischemic heart disease. Copyright © 2018 John Wiley & Sons, Ltd.

How UV Light Touches the Brain and Endocrine System Through Skin, and Why.

PubMed

Slominski, Andrzej T; Zmijewski, Michal A; Plonka, Przemyslaw M; Szaflarski, Jerzy P; Paus, Ralf

2018-05-01

The skin, a self-regulating protective barrier organ, is empowered with sensory and computing capabilities to counteract the environmental stressors to maintain and restore disrupted cutaneous homeostasis. These complex functions are coordinated by a cutaneous neuro-endocrine system that also communicates in a bidirectional fashion with the central nervous, endocrine, and immune systems, all acting in concert to control body homeostasis. Although UV energy has played an important role in the origin and evolution of life, UV absorption by the skin not only triggers mechanisms that defend skin integrity and regulate global homeostasis but also induces skin pathology (e.g., cancer, aging, autoimmune responses). These effects are secondary to the transduction of UV electromagnetic energy into chemical, hormonal, and neural signals, defined by the nature of the chromophores and tissue compartments receiving specific UV wavelength. UV radiation can upregulate local neuroendocrine axes, with UVB being markedly more efficient than UVA. The locally induced cytokines, corticotropin-releasing hormone, urocortins, proopiomelanocortin-peptides, enkephalins, or others can be released into circulation to exert systemic effects, including activation of the central hypothalamic-pituitary-adrenal axis, opioidogenic effects, and immunosuppression, independent of vitamin D synthesis. Similar effects are seen after exposure of the eyes and skin to UV, through which UVB activates hypothalamic paraventricular and arcuate nuclei and exerts very rapid stimulatory effects on the brain. Thus, UV touches the brain and central neuroendocrine system to reset body homeostasis. This invites multiple therapeutic applications of UV radiation, for example, in the management of autoimmune and mood disorders, addiction, and obesity.

Neuroendocrine Factors in the Regulation of Inflammation: Excessive Adiposity and Calorie Restriction

PubMed Central

Fontana, Luigi

2009-01-01

Acute inflammation is usually a self-limited life preserving response, triggered by pathogens and/or traumatic injuries. This transient response normally leads to removal of harmful agents and to healing of the damaged tissues. In contrast, unchecked or chronic inflammation can lead to persistent tissue and organ damage by activated leukocytes, cytokines, or collagen deposition. Excessive energy intake and adiposity cause systemic inflammation, whereas calorie restriction without malnutrition exerts a potent anti-inflammatory effect. As individuals accumulate fat and their adipocytes enlarge, adipose tissue undergoes molecular and cellular alterations, macrophages accumulate, and inflammation ensues. Overweight/obese subjects have significantly higher plasma concentrations of C-reactive protein and several cytokines, including IL-6, IL-8, IL-18, and TNF-alpha. Experimental animals on a chronic CR regimen, instead, have low levels of circulating inflammatory cytokines, low blood lymphocyte levels, reduced production of inflammatory cytokines by the white blood cells in response to stimulation, and cortisol levels in the high normal range. Recent data demonstrate that CR exerts a powerful anti-inflammatory effect also in non-human primates and humans. Multiple metabolic and neuroendocrine mechanisms are responsible for the CR-mediated anti-inflammatory effects, including reduced adiposity and secretion of pro-inflammatory adipokines, enhanced glucocorticoid production, reduced plasma glucose and advanced glycation end-product concentrations, increased parasympathetic tone, and increased ghrelin production. Measuring tissue specific effects of CR using genomic, proteomic and metabolomic techniques in humans will foster the understanding of the complex biological processes involved in the anti-inflammatory and anti-aging effects of CR. PMID:18502597

Uhthoff`s phenomenon 125 years later - what do we know today?

PubMed Central

Opara, JA; Brola, W; Wylegala, AA; Wylegala, E

2016-01-01

125 years have passed since Wilhelm Uhthoff reported the symptoms he observed after an increased body temperature from physical exertion. Those symptoms, which might have led to the transient impairment of vision in patients with Multiple Sclerosis and also observed in optic neuritis, were later named after him "Uhthoff's phenomenon". This has defined the strategy of rehabilitation procedures in Multiple Sclerosis for more than 100 years, restricting the use of thermal treatments and the possibility of aerobic exercises. The current state of knowledge concerning the Uhthoff's phenomenon and its influence on comprehensive rehabilitation in Multiple Sclerosis were presented in the current review report. PMID:27974923

Inhibition of cell-mediated immunity by the histone deacetylase inhibitor vorinostat: implications for therapy of cutaneous T-cell lymphoma.

PubMed

Stephen, Sasha; Morrissey, Kelly A; Benoit, Bernice M; Kim, Ellen J; Vittorio, Carmela C; Nasta, Sunita D; Showe, Louise C; Wysocka, Maria; Rook, Alain H

2012-02-01

Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was monitored for drug-induced immunosuppression while undergoing treatment with vorinostat. Analysis of the patient's natural killer cell function before and after initiation of treatment confirmed inhibition of this important cell-mediated immune function. In addition, the in vitro effects of vorinostat on the immunity of healthy volunteers confirmed that this class of drug can profoundly suppress multiple arms of the cellular immune response. These findings raise concerns of increased susceptibility to infection in this high-risk population.

Neural control of renal function in health and disease.

PubMed

DiBona, G F

1994-04-01

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

The Mechanisms of Manual Therapy in the Treatment of Musculoskeletal Pain: A Comprehensive Model

PubMed Central

Bialosky, Joel E; Bishop, Mark D; Price, Don D; Robinson, Michael E; George, Steven Z

2009-01-01

Prior studies suggest manual therapy (MT) as effective in the treatment of musculoskeletal pain; however, the mechanisms through which MT exerts its effects are not established. In this paper we present a comprehensive model to direct future studies in MT. This model provides visualization of potential individual mechanisms of MT that the current literature suggests as pertinent and provides a framework for the consideration of the potential interaction between these individual mechanisms. Specifically, this model suggests that a mechanical force from MT initiates a cascade of neurophysiological responses from the peripheral and central nervous system which are then responsible for the clinical outcomes. This model provides clear direction so that future studies may provide appropriate methodology to account for multiple potential pertinent mechanisms. PMID:19027342

Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

PubMed

Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

2016-10-01

Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

PubMed Central

Locri, Filippo; Amato, Rosario; Marsili, Stefania; Rusciano, Dario; Bagnoli, Paola

2018-01-01

Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role. PMID:29517994

Natural Antioxidants: Multiple Mechanisms to Protect Skin From Solar Radiation

PubMed Central

Dunaway, Spencer; Odin, Rachel; Zhou, Linli; Ji, Liyuan; Zhang, Yuhang; Kadekaro, Ana L.

2018-01-01

Human skin exposed to solar ultraviolet radiation (UVR) results in a dramatic increase in the production of reactive oxygen species (ROS). The sudden increase in ROS shifts the natural balance toward a pro-oxidative state, resulting in oxidative stress. The detrimental effects of oxidative stress occur through multiple mechanisms that involve alterations to proteins and lipids, induction of inflammation, immunosuppression, DNA damage, and activation of signaling pathways that affect gene transcription, cell cycle, proliferation, and apoptosis. All of these alterations promote carcinogenesis and therefore, regulation of ROS levels is critical to the maintenance of normal skin homeostasis. Several botanical products have been found to exhibit potent antioxidant capacity and the ability to counteract UV-induced insults to the skin. These natural products exert their beneficial effects through multiple pathways, including some known to be negatively affected by solar UVR. Aging of the skin is also accelerated by UVR exposure, in particular UVA rays that penetrate deep into the epidermis and the dermis where it causes the degradation of collagen and elastin fibers via oxidative stress and activation of matrix metalloproteinases (MMPs). Because natural compounds are capable of attenuating some of the UV-induced aging effects in the skin, increased attention has been generated in the area of cosmetic sciences. The focus of this review is to cover the most prominent phytoproducts with potential to mitigate the deleterious effects of solar UVR and suitability for use in topical application. PMID:29740318

Protective effects of melittin on transforming growth factor-{beta}1 injury to hepatocytes via anti-apoptotic mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Woo-Ram; Park, Ji-Hyun; Kim, Kyung-Hyun

Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases. In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-{beta}1-induced apoptosis in hepatocytes. TGF-{beta}1-treated hepatocytesmore » were exposed to low doses (0.5 and 1 {mu}g/mL) and high dose (2 {mu}g/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-{beta}1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-{beta}1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results demonstrate that TGF-{beta}1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-{beta}1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-{beta}1-mediated injury. - Highlights: > We investigated the anti-apoptotic effect of melittin on TGF-{beta}1-induced hepatocyte. > TGF-{beta}1 induces hepatocyte apoptosis. > TGF-{beta}1-treated hepatocytes were exposed to low doses and high dose of melittin. > Optimal dose of melittin exerts anti-apoptotic effects to hepatocytes.« less

Net carbon uptake has increased through warming-induced changes in temperate forest phenology

Treesearch

Trevor F. Keenan; Josh Gray; Mark A. Friedl; Michael Toomey; Gil Bohrer; David Y. Hollinger; J. William Munger; John O’Keefe; Hans Peter Schmid; Ian Sue Wing; Bai Yang; Andrew D. Richardson

2014-01-01

The timing of phenological events exerts a strong control over ecosystem function and leads to multiple feedbacks to the climate system1. Phenology is inherently sensitive to temperature (although the exact sensitivity is disputed2) and recent warming is reported to have led to earlier spring, later autumn3,4...

Textbook Presentations of Weight: Conceptual Difficulties and Language Ambiguities

ERIC Educational Resources Information Center

Taibu, Rex; Rudge, David; Schuster, David

2015-01-01

The term "weight" has multiple related meanings in both scientific and everyday usage. Even among experts and in textbooks, weight is ambiguously defined as either the gravitational force on an object or operationally as the magnitude of the force an object exerts on a measuring scale. This poses both conceptual and language difficulties…

Project Physics Tests 2, Motion in the Heavens.

ERIC Educational Resources Information Center

Harvard Univ., Cambridge, MA. Harvard Project Physics.

Test items relating to Project Physics Unit 2 are presented in this booklet. Included are 70 multiple-choice and 22 problem-and-essay questions. Concepts of motion in the heavens are examined for planetary motions, heliocentric theory, forces exerted on the planets, Kepler's laws, gravitational force, Galileo's work, satellite orbits, Jupiter's…

The effect of vocal and instrumental music on cardio respiratory variables, energy expenditure and exertion levels during sub maximal treadmill exercise.

PubMed

Savitha, D; Sejil, T V; Rao, Shwetha; Roshan, C J; Roshan, C J

2013-01-01

The purpose of the study was to investigate the effect of vocal and instrumental music on various physiological parameters during submaximal exercise. Each subject underwent three sessions of exercise protocol without music, with vocal music, and instrumental versions of same piece of music. The protocol consisted of 10 min treadmill exercise at 70% HR(max) and 20 min of recovery. Minute to minute heart rate and breath by breath recording of respiratory parameters, rate of energy expenditure and perceived exertion levels were measured. Music, irrespective of the presence or absence of lyrics, enabled the subjects to exercise at a significantly lower heart rate and oxygen consumption, reduced the metabolic cost and perceived exertion levels of exercise (P < 0.05). There was faster recovery of systolic and diastolic blood pressures and exertion levels during the post exercise period. Music having a relaxant effect could have probably increased the parasympathetic activation leading to these effects.

Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

PubMed Central

Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

2016-01-01

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA. PMID:27827907

Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats.

PubMed

Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

2016-11-04

Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N -ethyl- N '-nitro- N -nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis.

PubMed

Wang, Junjuan; Wang, Jiaqiu; Lu, Ping; Cai, Youzhi; Wang, Yafei; Hong, Lan; Ren, Hao; Heng, Boon Chin; Liu, Hua; Zhou, Jing; Ouyang, Hongwei

2015-09-01

FTY720 has recently been approved as an oral drug for treating relapsing forms of multiple sclerosis, and exerts its therapeutic effect by acting as an immunological inhibitor targeting the sphingosine-1-phosphate (S1P) receptor subtype (S1P1) of T cells. Recently studies demonstrated positive efficacy of this drug on spinal cord injury (SCI) in animal models after systemic administration, albeit with significant adverse side effects. We hereby hypothesize that localized delivery of FTY720 can promote SCI recovery by reducing pathological astrogliosis. The mechanistic functions of FTY720 were investigated in vitro and in vivo utilizing immunofluorescence, histology, MRI and behavioral analysis. The in vitro study showed that FTY720 can reduce astrocyte migration and proliferation activated by S1P. FTY720 can prolong internalization of S1P1 and exert antagonistic effects on S1P1. In vivo study of SCI animal models demonstrated that local delivery of FTY720 with polycaprolactone (PCL) membrane significantly decreased S1P1 expression and glial scarring compared with the control group. Furthermore, FTY720-treated groups exhibited less cavitation volume and neuron loss, which significantly improved recovery of motor function. These findings demonstrated that localized delivery of FTY720 can promote SCI recovery by targeting the S1P1 receptor of astrocytes, provide a new therapeutic strategy for SCI treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiple mediation path model of pain's cascading influence on physical disability in individuals with SCI from Colombia, South America.

PubMed

Perrin, Paul B; Paredes, Alejandra Morlett; Olivera, Silvia Leonor; Lozano, Juan Esteban; Leal, Wendy Tatiana; Ahmad, Usman F; Arango-Lasprilla, Juan Carlos

2017-01-01

Research has begun to document the bivariate connections between pain in individuals with spinal cord injury (SCI) and various aspects of health related quality of life (HRQOL), such as fatigue, social functioning, mental health, and physical functioning. The purpose of this study was to construct and test a theoretical path model illuminating the stage-wise and sequential (cascading) HRQOL pathways through which pain increases physical disability in individuals with SCI in a sample from Colombia, South America. It was hypothesized that increased pain would lead to decreased energy, which would lead to decreased mental health and social functioning, which both would lead to emotional role limitations, which finally would lead to physical role limitations. A cross-sectional study assessed individuals with SCI (n = 40) in Neiva, Colombia. Participants completed a measure indexing various aspects of HRQOL. The path model overall showed excellent fit indices, and each individual path within the model was statistically significant. Pain exerted significant indirect effects through all possible mediators in the model, ultimately suggesting that energy, mental health, social functioning, and role limitations-emotional were likely pathways through which pain exerted its effects on physical disability in individuals with SCI. These findings uncover several potential nodes for clinical intervention which if targeted in the context of rehabilitation or outpatient services, could result in salubrious direct and indirect effects reverberating down the theoretical causal chain and ultimately reducing physical disability in individuals with SCI.

Exertion Testing in Youth with Mild Traumatic Brain Injury/Concussion.

PubMed

Dematteo, Carol; Volterman, Kimberly A; Breithaupt, Peter G; Claridge, Everett A; Adamich, John; Timmons, Brian W

2015-11-01

The decision regarding return to activity (RTA) after mild traumatic brain injuries/concussion is one of the most difficult and controversial areas in concussion management, particularly for youth. This study investigated how youth with postconcussion syndrome (PCS) are affected by exertion and whether standardized exertion testing using the McMaster All-Out Progressive Continuous Cycling Test can contribute to clinical decision making for safe RTA. Fifty-four youth (8.5-18.3 yr) with a previously confirmed concussion participated in the study. Each participant performed exertion testing on a cycle ergometer and completed a Postconcussion Symptom scale at the following time points: before exertion (baseline), 5 and 30 min, and 24 h after exertion. A modified Postconcussion Symptom scale was administered at 2-min intervals during exertion. Participants had a mean ± SD symptom duration of 6.3 ± 6.9 months after the most recent concussive injury, with a median of 4.1 months (range, 0.7-35 months). Sixty-three percent of participants had symptoms during exertion testing. Symptom profile (number and severity) significantly affected perception of exertion at 50% peak mechanical power. During acute assessment of symptoms (30-min after exertion), headache (P = 0.39), nausea (P = 0.63), and dizziness (P = 0.35) did not change. However, both the number and severity of symptoms significantly improved over 24 h, with 56.8% of youth showing improvements. The time from the most recent injury had a significant effect on the symptom score at baseline, 30 min after exertion, and 24 h after exertion. Exertion testing has an important role in the evaluation of symptoms and readiness to RTA, particularly in youth who are slow to recover. Overall, controlled exertion seemed to lesson symptoms for most youth.

Development and Application of a Virtual Screening Protocol for the Identification of Multitarget Fragments.

PubMed

Bottegoni, Giovanni; Veronesi, Marina; Bisignano, Paola; Kacker, Puneet; Favia, Angelo D; Cavalli, Andrea

2016-06-20

In this study, we report on a virtual ligand screening protocol optimized to identify fragments endowed with activity at multiple targets. Thanks to this protocol, we were able to identify a fragment that displays activity in the low-micromolar range at both β-secretase 1 (BACE-1) and glycogen synthase kinase 3β (GSK-3β). These two structurally and physiologically unrelated enzymes likely contribute, through different pathways, to the onset of Alzheimer's disease (AD). Therefore, their simultaneous inhibition holds great potential in exerting a profound effect on AD. In perspective, the strategy outlined herein can be adapted to other target combinations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, migration effects and accelerates cell cycle progression in multiple myeloma cells via activating the Akt pathway.

PubMed

Zheng, Dong; Chen, Ziang; Chen, Jingfu; Zhuang, Xiaomin; Feng, Jianqiang; Li, Juan

2016-10-01

Hydrogen sulfide (H2S), regarded as the third gaseous transmitter, mediates and induces various biological effects. The present study investigated the effects of H2S on multiple myeloma cell progression via amplifying the activation of Akt pathway in multiple myeloma cells. The level of H2S produced in multiple myeloma (MM) patients and healthy subjects was measured using enzyme-linked immunosorbent assay (ELISA). MM cells were treated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated-Akt (p-Akt), Bcl-2 and caspase-3 were measured by western blot assay. Cell viability was detected by Cell Counting Kit 8 (CCK-8). The cell cycle was analyzed by flow cytometry. Our results show that the concentration of H2S was higher in MM patients and that it increased in parallel with disease progression. Treating MM cells with 500 µmol/l NaHS for 24 h markedly increased the expression level of Bcl-2 and the activation of p-Akt, however, the expression level of caspase-3 was decreased, cell viability was increased, and cell cycle progression was accelerated in MM cells. NaHS also induced migration in MM cells in transwell migration assay. Furthermore, co-treatment of MM cells with 500 µmol/l NaHS and 50 µmol/l LY294002 for 24 h significantly overset these effects. In conclusion, our findings demonstrate that the Akt pathway contributes to NaHS-induced cell proliferation, migration and acceleration of cell cycle progression in MM cells.

Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells.

PubMed

Zhou, Xiuxia; Su, Jingna; Feng, Shaoyan; Wang, Lixia; Yin, Xuyuan; Yan, Jingzhe; Wang, Zhiwei

2016-11-29

Pancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor function in a variety of human cancers including PC, via targeting multiple therapeutically important cancer signaling pathways. However, the detailed molecular mechanisms are not fully understood. Two transcriptional co-activators, YAP (Yes-associated protein) and its close paralog TAZ (transcriptional coactivator with PDZ-binding motif) exert oncogenic activities in various cancers. Therefore, in this study we aimed to determine the molecular basis of curcumin-induced cell proliferation inhibition in PC cells. First, we detected the anti-tumor effects of curcumin on PC cell lines using CTG assay, Flow cytometry, clonogenic assay, wound healing assay and Transwell invasion assay. We found that curcumin significantly suppressed cell growth, weakened clonogenic potential, inhibited migration and invasion, and induced apoptosis and cell cycle arrest in PC cells. We further measured that overexpression of YAP enhanced cell proliferation and abrogated the cytotoxic effects of curcumin on PC cells. Moreover, we found that curcumin markedly down-regulated YAP and TAZ expression and subsequently suppressed Notch-1 expression. Collectively, these findings suggest that pharmacological inhibition of YAP and TAZ activity may be a promising anticancer strategy for the treatment of PC patients.

Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells

PubMed Central

Wang, Lixia; Yin, Xuyuan; Yan, Jingzhe; Wang, Zhiwei

2016-01-01

Pancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor function in a variety of human cancers including PC, via targeting multiple therapeutically important cancer signaling pathways. However, the detailed molecular mechanisms are not fully understood. Two transcriptional co-activators, YAP (Yes-associated protein) and its close paralog TAZ (transcriptional coactivator with PDZ-binding motif) exert oncogenic activities in various cancers. Therefore, in this study we aimed to determine the molecular basis of curcumin-induced cell proliferation inhibition in PC cells. First, we detected the anti-tumor effects of curcumin on PC cell lines using CTG assay, Flow cytometry, clonogenic assay, wound healing assay and Transwell invasion assay. We found that curcumin significantly suppressed cell growth, weakened clonogenic potential, inhibited migration and invasion, and induced apoptosis and cell cycle arrest in PC cells. We further measured that overexpression of YAP enhanced cell proliferation and abrogated the cytotoxic effects of curcumin on PC cells. Moreover, we found that curcumin markedly down-regulated YAP and TAZ expression and subsequently suppressed Notch-1 expression. Collectively, these findings suggest that pharmacological inhibition of YAP and TAZ activity may be a promising anticancer strategy for the treatment of PC patients. PMID:27738325

Hydrocortisone Infusion Exerts Dose- and Sex-Dependent Effects on Attention to Emotional Stimuli

ERIC Educational Resources Information Center

Breitberg, Alaina; Drevets, Wayne C.; Wood, Suzanne E.; Mah, Linda; Schulkin, Jay; Sahakian, Barbara J.; Erickson, Kristine

2013-01-01

Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to…

MIBE acts as antagonist ligand of both estrogen receptor α and GPER in breast cancer cells

PubMed Central

2012-01-01

Introduction The multiple biological responses to estrogens are mainly mediated by the classical estrogen receptors ERα and ERβ, which act as ligand-activated transcription factors. ERα exerts a main role in the development of breast cancer; therefore, the ER antagonist tamoxifen has been widely used although its effectiveness is limited by de novo and acquired resistance. Recently, GPR30/GPER, a member of the seven-transmembrane G protein-coupled receptor family, has been implicated in mediating the effects of estrogens in various normal and cancer cells. In particular, GPER triggered gene expression and proliferative responses induced by estrogens and even ER antagonists in hormone-sensitive tumor cells. Likewise, additional ER ligands showed the ability to bind to GPER eliciting promiscuous and, in some cases, opposite actions through the two receptors. We synthesized a novel compound (ethyl 3-[5-(2-ethoxycarbonyl-1-methylvinyloxy)-1-methyl-1H-indol-3-yl]but-2-enoate), referred to as MIBE, and investigated its properties elicited through ERα and GPER in breast cancer cells. Methods Molecular modeling, binding experiments and functional assays were performed in order to evaluate the biological action exerted by MIBE through ERα and GPER in MCF7 and SkBr3 breast cancer cells. Results MIBE displayed the ability to act as an antagonist ligand for ERα and GPER as it elicited inhibitory effects on gene transcription and growth effects by binding to both receptors in breast cancer cells. Moreover, GPER was required for epidermal growth factor receptor (EGFR) and ERK activation by EGF as ascertained by using MIBE and performing gene silencing experiments. Conclusions Our findings provide novel insights on the functional cross-talk between GPER and EGFR signaling. Furthermore, the exclusive antagonistic activity exerted by MIBE on ERα and GPER could represent an innovative pharmacological approach targeting breast carcinomas which express one or both receptors at the beginning and/or during tumor progression. Hence, the simultaneous inhibition of both ERα and GPER may guarantee major therapeutic benefits in respect to the use of a selective estrogen receptor antagonist. PMID:22251451

MIBE acts as antagonist ligand of both estrogen receptor α and GPER in breast cancer cells.

PubMed

Lappano, Rosamaria; Santolla, Maria Francesca; Pupo, Marco; Sinicropi, Maria Stefania; Caruso, Anna; Rosano, Camillo; Maggiolini, Marcello

2012-01-17

The multiple biological responses to estrogens are mainly mediated by the classical estrogen receptors ERα and ERβ, which act as ligand-activated transcription factors. ERα exerts a main role in the development of breast cancer; therefore, the ER antagonist tamoxifen has been widely used although its effectiveness is limited by de novo and acquired resistance. Recently, GPR30/GPER, a member of the seven-transmembrane G protein-coupled receptor family, has been implicated in mediating the effects of estrogens in various normal and cancer cells. In particular, GPER triggered gene expression and proliferative responses induced by estrogens and even ER antagonists in hormone-sensitive tumor cells. Likewise, additional ER ligands showed the ability to bind to GPER eliciting promiscuous and, in some cases, opposite actions through the two receptors. We synthesized a novel compound (ethyl 3-[5-(2-ethoxycarbonyl-1-methylvinyloxy)-1-methyl-1H-indol-3-yl]but-2-enoate), referred to as MIBE, and investigated its properties elicited through ERα and GPER in breast cancer cells. Molecular modeling, binding experiments and functional assays were performed in order to evaluate the biological action exerted by MIBE through ERα and GPER in MCF7 and SkBr3 breast cancer cells. MIBE displayed the ability to act as an antagonist ligand for ERα and GPER as it elicited inhibitory effects on gene transcription and growth effects by binding to both receptors in breast cancer cells. Moreover, GPER was required for epidermal growth factor receptor (EGFR) and ERK activation by EGF as ascertained by using MIBE and performing gene silencing experiments. Our findings provide novel insights on the functional cross-talk between GPER and EGFR signaling. Furthermore, the exclusive antagonistic activity exerted by MIBE on ERα and GPER could represent an innovative pharmacological approach targeting breast carcinomas which express one or both receptors at the beginning and/or during tumor progression. Hence, the simultaneous inhibition of both ERα and GPER may guarantee major therapeutic benefits in respect to the use of a selective estrogen receptor antagonist.

Chronic Exertional Compartment Syndrome.

PubMed

Braver, Richard T

2016-04-01

Increased tissue pressure within a fascial compartment may be the result from any increase in volume within its contents, or any decrease in size of the fascial covering or its distensibility. This may lead to symptoms of leg tightness, pain or numbness brought about by exercise. There are multiple differential diagnoses of exercise induced leg pain and the proper diagnoses of chronic exertional compartment syndrome (CECS) is made by a careful history and by exclusion of other maladies and confirmed by compartment syndrome testing as detailed in this text. Surgical fasciotomies for the anterior, lateral, superficial and deep posterior compartments are described in detail along with ancillary procedures for chronic shin splints that should allow the athlete to return to competitive activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis.

PubMed

Rakanović-Todić, Maida; Burnazović-Ristić, Lejla; Ibrulj, Slavka; Mulbegović, Nedžad

2014-05-01

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS). The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 μg/mL). However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted.

Pseudolaric acid B attenuates atherosclerosis progression and inflammation by suppressing PPARγ-mediated NF-κB activation.

PubMed

Li, Tan; Wang, Wei; Li, Yu-Xiu; Li, Xiao; Ji, Wen-Jie; Ma, Yong-Qiang; Chen, Hong; Zhao, Ji-Hong; Zhou, Xin

2018-06-01

Atherosclerosis is a progressive disease of large arteries characterized with chronic inflammation and aberrant immune response. Pseudolaric acid B (PB) has been found to exert multiple effects by inhibiting inflammatory response. However, there is no comprehensive assessment of the effects of PB on atherosclerosis using relevant in vivo and in vitro models. Male ApoE -/- mice were treated with PB orally with a high fat diet (HFD) to clarify its anti-atherosclerotic activities. RAW264.7 macrophage line, a well-accepted cell model of atherosclerosis, was used to investigate anti-inflammatory effects and molecular mechanisms of PB. PB significantly attenuated atherosclerotic lesions by modulating plasma lipid profiles as well as inhibiting inflammatory responses in macrophages of atherosclerotic mice. Meanwhile, PB markedly suppressed the expression of pro-inflammatory cytokines, and regulated cholesterol efflux related genes in oxidative low density lipoprotein (ox-LDL)-loaded macrophages. The cellular uptake of Dil-labeled ox-LDL was significantly inhibited by PB either. Moreover, the ability of PB to suppress nuclear factor kappa B (NF-κB) and activate peroxisome proliferator-activated receptor gamma (PPARγ) was confirmed using luciferase reporter assays. Conversely, the selective PPARγ antagonist GW9662 reversed the influence of PB in macrophages. Together, these findings indicate that PB exerts its protective effects on atherosclerosis by inhibiting macrophage-mediated inflammatory response and cellular ox-LDL uptake, and promoting cholesterol efflux by suppressing NF-κB activation PPARγ-dependently. Therefore, PB may be a promising agent for inflammatory and atherosclerotic diseases. Copyright © 2018. Published by Elsevier B.V.

Adiponectin limits monocytic microparticle-induced endothelial activation by modulation of the AMPK, Akt and NFκB signaling pathways.

PubMed

Ehsan, Mehroz; Singh, Krishna K; Lovren, Fina; Pan, Yi; Quan, Adrian; Mantella, Laura-Eve; Sandhu, Paul; Teoh, Hwee; Al-Omran, Mohammed; Verma, Subodh

2016-02-01

Monocyte-derived microparticles (mono-MPs) are emerging as critical transducers of inflammatory signals, and have been suggested to link cardiovascular risk factors to vascular injury. Since adiponectin has been proposed to exert multiple anti-inflammatory and vasculoprotective effects, we hypothesized that it might serve to limit the production and/or action of mono-MPs. Flow cytometry and western blot studies were conducted on THP-1 cells, THP-1-derived MPs, human umbilical vein endothelial cells (HUVECs), peripheral blood CD14+ monocytes and mice to evaluate the effects of adiponectin on mono-MPs. Adiponectin attenuated lipopolysaccharide (LPS)-evoked MP release from THP-1 monocytes (30% difference) and peripheral blood monocytes (both P < 0.05) as well as dampened LPS-induced mono-MP generation in vivo. Furthermore, peritoneal monocytes from Adipoq(-/-) mice generated significantly greater MPs than those from Adipoq(+/+) littermates in the absence (2.3 fold difference, P < 0.05) and presence (1.6 fold difference, P < 0.05) of LPS. LPS-induced MP expression of NLRP3 inflammasome and its key components, namely cleaved ASC, caspase-1 and IL-1β (pro- and cleaved), were markedly attenuated by adiponectin. HUVECs incubated with MPs from LPS-treated THP-1 cells exhibited increased VCAM-1 levels and adhesion to THP-1 cells. Adiponectin abrogated these effects. From a mechanistic standpoint, the effects of adiponectin on MP release and molecular signaling occurred at least in part through the AMPK, Akt and NFκB pathways. Adiponectin exerts novel effects to limit the production and action of mono-MPs, underscoring yet another pleiotropic effect of this adipokine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effect of ferulic acid ethyl ester on leptin-induced proliferation and migration of aortic smooth muscle cells.

PubMed

Tsai, Yung-Chieh; Lee, Yen-Mei; Hsu, Chih-Hsiung; Leu, Sy-Ying; Chiang, Hsiao-Yen; Yen, Mao-Hsiung; Cheng, Pao-Yun

2015-08-28

Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), β-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml(-1)) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 μM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, β-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml(-1)) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 μM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease.

The effect of ferulic acid ethyl ester on leptin-induced proliferation and migration of aortic smooth muscle cells

PubMed Central

Tsai, Yung-Chieh; Lee, Yen-Mei; Hsu, Chih-Hsiung; Leu, Sy-Ying; Chiang, Hsiao-Yen; Yen, Mao-Hsiung; Cheng, Pao-Yun

2015-01-01

Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), β-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml−1) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 μM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, β-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml−1) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 μM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease. PMID:26315599

Simultaneous Retrieval of Multiple Aerosol Parameters Using a Multi-Angular Approach

NASA Technical Reports Server (NTRS)

Kuo, K.-S.; Weger, R. C.; Welch, R. M.

1997-01-01

Atmospheric aerosol particles, both natural and anthropogenic, are important to the earth's radiative balance through their direct and indirect effects. They scatter the incoming solar radiation (direct effect) and modify the shortwave reflective properties of clouds by acting as cloud condensation nuclei (indirect effect). Although it has been suggested that aerosols exert a net cooling influence on climate, this effect has received less attention than the radiative forcing due to clouds and greenhouse gases. In order to understand the role that aerosols play in a changing climate, detailed and accurate observations are a prerequisite. The retrieval of aerosol optical properties by satellite remote sensing has proven to be a difficult task. The difficulty results mainly from the tenuous nature and variable composition of aerosols. To date, with single-angle satellite observations, we can only retrieve reliably against dark backgrounds, such as over oceans and dense vegetation. Even then, assumptions must be made concerning the chemical composition of aerosols. In this investigation we examine the feasibility of simultaneous retrieval of multiple aerosol optical parameters using reflectances from a typical set of twelve angles observed by the French POLDER instrument. The retrieved aerosol optical parameters consist of asymmetry factor, single scattering albedo, surface albedo, and optical thickness.

Biological activity of selenium: Revisited.

PubMed

Wrobel, Jagoda K; Power, Ronan; Toborek, Michal

2016-02-01

Selenium (Se) is an essential micronutrient that exerts multiple and complex effects on human health. Se is essential for human well-being largely due to its potent antioxidant, anti-inflammatory, and antiviral properties. The physiological functions of Se are carried out by selenoproteins, in which Se is specifically incorporated as the amino acid, selenocysteine. Importantly, both beneficial and toxic effects of Se have been reported suggesting that the mode of action of Se is strictly chemical form and concentration dependent. Additionally, there is a relatively narrow window between Se deficiency and toxicity and growing evidence suggests that Se health effects depend greatly on the baseline level of this micronutrient. Thus, Se supplementation is not an easy task and requires an individualized approach. It is essential that we continue to explore and better characterize Se containing compounds and mechanisms of action, which could be crucial for disease prevention and treatment. © 2015 International Union of Biochemistry and Molecular Biology.

Heme-mediated cell activation: the inflammatory puzzle of sickle cell anemia.

PubMed

Guarda, Caroline Conceição da; Santiago, Rayra Pereira; Fiuza, Luciana Magalhães; Aleluia, Milena Magalhães; Ferreira, Júnia Raquel Dutra; Figueiredo, Camylla Vilas Boas; Yahouedehou, Setondji Cocou Modeste Alexandre; Oliveira, Rodrigo Mota de; Lyra, Isa Menezes; Gonçalves, Marilda de Souza

2017-06-01

Hemolysis triggers the onset of several clinical manifestations of sickle cell anemia (SCA). During hemolysis, heme, which is derived from hemoglobin (Hb), accumulates due to the inability of detoxification systems to scavenge sufficiently. Heme exerts multiple harmful effects, including leukocyte activation and migration, enhanced adhesion molecule expression by endothelial cells and the production of pro-oxidant molecules. Area covered: In this review, we describe the effects of heme on leukocytes and endothelial cells, as well as the features of vascular endothelial cells related to vaso-occlusion in SCA. Expert commentary: Free Hb, heme and iron, potent cytotoxic intravascular molecules released during hemolysis, can exacerbate, modulate and maintain the inflammatory response, a main feature of SCA. Endothelial cells in the vascular environment, as well as leukocytes, can become activated via the molecular signaling effects of heme. Due to the hemolytic nature of SCA, hemolysis represents an interesting therapeutic target for heme-scavenging purposes.

Protective effect of Panax ginseng in cisplatin-induced cachexia in rats.

PubMed

Lobina, Carla; Carai, Mauro A M; Loi, Barbara; Gessa, Gian Luigi; Riva, Antonella; Cabri, Walter; Petrangolini, Giovanna; Morazzoni, Paolo; Colombo, Giancarlo

2014-05-01

This study investigated the protective effect of a standardized extract of Panax ginseng on multiple cisplatin-induced 'sickness behaviors' (model of cancer-induced cachexia) in rats. Cisplatin was administered twice weekly (1-2 mg/kg, intraperitoneal) for 5 consecutive weeks. Panax ginseng extract (0, 25 and 50 mg/kg, intragastric) was administered daily over the 5-week period of cisplatin exposure. Malaise, bodyweight and temperature, pain sensitivity, and endurance running were recorded at baseline and at 5 weekly intervals. Treatment with cisplatin produced severe signs of malaise, marked loss of bodyweight, hypothermia, hyperalgesia and reduction in running time. Treatment with Panax ginseng extract completely prevented all cisplatin-induced alterations. These data indicate that treatment with Panax ginseng extract exerted a protective effect in a rat model of cachexia and suggest that Panax ginseng extract may be a therapeutic promising tool for supportive care in oncology.

Genetics and Genomics of Single-Gene Cardiovascular Diseases: Common Hereditary Cardiomyopathies as Prototypes of Single-Gene Disorders

PubMed Central

Marian, Ali J.; van Rooij, Eva; Roberts, Robert

2016-01-01

This is the first of 2 review papers on genetics and genomics appearing as part of the series on “omics.” Genomics pertains to all components of an organism’s genes, whereas genetics involves analysis of a specific gene(s) in the context of heredity. The paper provides introductory comments, describes the basis of human genetic diversity, and addresses the phenotypic consequences of genetic variants. Rare variants with large effect sizes are responsible for single-gene disorders, whereas complex polygenic diseases are typically due to multiple genetic variants, each exerting a modest effect size. To illustrate the clinical implications of genetic variants with large effect sizes, 3 common forms of hereditary cardiomyopathies are discussed as prototypic examples of single-gene disorders, including their genetics, clinical manifestations, pathogenesis, and treatment. The genetic basis of complex traits is discussed in a separate paper. PMID:28007145

[Progress of researches on the mechanism of cupping therapy].

PubMed

Cui, Shuai; Cui, Jin

2012-12-01

Cupping therapy of Chinese medicine is able to relieve a variety of diseases or clinical conditions, which results from the comprehensive effects of multiple types of stimulation exerted onto the regional acupoint areas. Among the stimuli, the negative pressure from cupping is one of the main factors inducing therapeutic effects. In the present paper, the authors review development of researches on the underlying mechanism of therapeutic effects of cupping-negative pressure from 1) the factor of intra-cup negative pressure; 2) influence of intra-cup negative pressure on cup-blackspot formation; 3) influence of cupping on regional blood vessels and blood flow; 4) effect of cupping on regional ultrastructure of the capillary in the raw-surface tissue; 5) effect of cupping-negative pressure on regional endothelial cells; and 6) biological effects of negative pressure drainage. Generally, cupping induced negative pressure can dilate local blood vessels to improve microcirculation, promote capillary endothelial cells repair, accelerate granulation and angiogenesis, etc., in the regional tissues, normalizing the patients' functional state at last.

Predictors of health-related quality of life among low-income midlife women.

PubMed

Ham, Ok Kyung

2011-02-01

The purpose of this study was to determine whether any of the sociodemographic, biomedical, psychosocial, and medical-care factors independently predict health-related quality of life (HRQoL) among low-income women. Cross-sectional data were used to predict factors that determine HRQoL. A survey was conducted targeting a convenience sample of 200 midlife women. Blood samples were drawn from all participants, who also received a physical examination. Hierarchical multiple regression analysis was used to test the independent effects of each factor. The study found that sociodemographic and psychosocial factors were independently associated with HRQoL. Compared to married women, widowed or divorced women had significantly lower HRQoL, whereas those with higher levels of stress perception and those not performing regular exercise had significantly lower HRQoL (p < .01). The full model accounted for 44.7% of the variance in HRQoL. The HRQoL of low-income midlife women was associated with multiple factors, with stress perception exerting the major influence.

Whose Hand Rocks the Cradle? Parallel Discourses in the Baby Room

ERIC Educational Resources Information Center

Powell, Sacha; Goouch, Kathy

2012-01-01

This article explores the practice narratives of a group of 25 caregivers who work with babies in daycare settings in England and seeks to illustrate awareness of, resistance to and compliance with powerful discourses. It is argued that multiple voices exert an influence over baby room practice, disempowering the caregivers and reducing their…

Position And Force Control For Multiple-Arm Robots

NASA Technical Reports Server (NTRS)

Hayati, Samad A.

1988-01-01

Number of arms increased without introducing undue complexity. Strategy and computer architecture developed for simultaneous control of positions of number of robot arms manipulating same object and of forces and torques that arms exert on object. Scheme enables coordinated manipulation of object, causing it to move along assigned trajectory and be subjected to assigned internal forces and torques.

Greece before the Bologna Process: Confronting or Embracing Quality Assurance in Higher Education?

ERIC Educational Resources Information Center

Stamoulas, Aristotelis

2006-01-01

The globalization of education, with its multiple associations with the growth of the knowledge society, the increasing penetration of market forces in higher education and the treatment of education as an exportable good, supplied in different forms and by various providers, exerts the need for systematic quality assurance in higher education. In…

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system.

PubMed

Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

2013-03-01

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

PubMed Central

Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

2013-01-01

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng’s therapeutic effects. These include Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng. PMID:23717153

Alkylating chemotherapy may exert a uniquely deleterious effect upon neo-antigen-targeting anticancer vaccination

PubMed Central

Litterman, Adam J; Dudek, Arkadiusz Z; Largaespada, David A

2013-01-01

Alkylating chemotherapy exerts both antineoplastic and immunostimulatory effects. However, in addition to depleting regulatory T cells (Treg), alkylating agents also mediate a long lasting antiproliferative effect on responder lymphocytes. Our recent findings indicate that this antiproliferative effect profoundly impairs vaccination-induced immune responses, especially in the case of vaccines that target specific tumor-associated neo-antigens that do not require Treg depletion. PMID:24251080

Effect of Carbohydrate Ingestion on Ratings of Perceived Exertion during a Marathon.

ERIC Educational Resources Information Center

Utter, Alan C.; Kang, Jie; Robertson, Robert J.; Nieman, David C.; Chaloupka, Edward C.; Suminski, Richard R.; Piccinni, Cristiana R.

2002-01-01

Investigated the effects of carbohydrate substrate availability on ratings of perceived exertion (RPE) and hormonal regulation during a competitive marathon. Data on marathon runners randomly assigned to receive carbohydrate or placebo indicated that those who ingested carbohydrate rather than placebo beverages were able to run at a higher…

Research progress on the anticancer effects of vitamin K2.

PubMed

Xv, Fan; Chen, Jiepeng; Duan, Lili; Li, Shuzhuang

2018-06-01

Despite the availability of multiple therapeutic methods for patients with cancer, the long-term prognosis is not satisfactory in a number of different cancer types. Vitamin K2 (VK2), which exerts anticancer effects on a number of cancer cell lines, is considered to be a prospective novel agent for the treatment of cancer. The present review aims to summarize the results of studies in which VK2 was administered either to patients with cancer or animals inoculated with cancerous cells, particularly investigating the inhibitory effects of VK2 on cancerous cells, primarily involving cell-cycle arrest, cell differentiation, apoptosis, autophagy and invasion. The present review summarizes evidence stating that treatment with VK2 could positively inhibit the growth of cancer cells, making it a potentially useful approach for the prevention and clinical treatment of cancer. Additionally, the combination treatment of VK2 and established chemotherapeutics may achieve better results, with fewer side effects. Therefore, more attention should be paid to the effects of micronutrients on tumors.

Structuring effects of chemicals from the sea fan Phyllogorgia dilatata on benthic communities.

PubMed

Ribeiro, Felipe V; da Gama, Bernardo A P; Pereira, Renato C

2017-01-01

Despite advances in understanding the ecological functions of secondary metabolites from marine organisms, there has been little focus on the influence of chemically-defended species at the community level. Several compounds have been isolated from the gorgonian octocoral Phyllogorgia dilatata , a conspicuous species that forms dense canopies on rocky reefs of northern Rio de Janeiro State, Brazil. Manipulative experiments were performed to study: (1) the effects of live colonies of P. dilatata (physical presence and chemistry) on recruitment of sympatric benthic organisms; (2) the allelopathic effects of its chemicals on competitors; and (3) chemotactic responses of the non-indigenous brittle star, Ophiothela mirabilis . Early establishment of benthic species was influenced on substrates around live P. dilatata colonies and some effects could be attributed to the gorgonian's secondary metabolites . In addition, the gorgonian chemicals also exerted an allelopathic effect on the sympatric zoanthid Palythoa caribaeorum, and positive chemotaxis upon O. mirabilis . These results indicate multiple ecological roles of a chemically-defended gorgonian on settlement, sympatric competitors, and non-indigenous species.

Anti-neuroinflammatory Effect of Emodin in LPS-Stimulated Microglia: Involvement of AMPK/Nrf2 Activation.

PubMed

Park, Sun Young; Jin, Mei Ling; Ko, Min Jung; Park, Geuntae; Choi, Young-Whan

2016-11-01

AMPK/Nrf2 signaling regulates multiple antioxidative factors and exerts neuroprotective effects. Emodin is one of the main bioactive components extracted from Polygonum multiflorum, a plant possessing important activities for human health and for treating a variety of diseases. This study examined whether emodin can activate AMPK/Nrf2 signaling and induce the expression of genes targeted by this pathway. In addition, the anti-neuroinflammatory properties of emodin in lipopolysaccharide (LPS)-stimulated microglia were examined. In microglia, the emodin treatment increased the levels of LKB1, CaMKII, and AMPK phosphorylation. Emodin increased the translocation and transactivity of Nrf2 and enhanced the levels of HO-1 and NQO1. In addition, the emodin-mediated expression of HO-1 and NQO1 was attenuated completely by an AMPK inhibitor (compound C). Moreover, emodin decreased dramatically the LPS-induced production of NO and PGE 2 as well as the protein expression and promoter activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, emodin effectively inhibited the production of pro-inflammatory cytokines, TNF-α and IL-6, and reduced the level of IκBα phosphorylation, leading to the suppression of the nuclear translocation, phosphorylation, and transactivity of NF-κB. Emodin also suppressed the LPS-stimulated activation of STATs, JNK, and p38 MAPK. The anti-inflammatory effects of emodin were reversed by transfection with Nrf-2 and HO-1 siRNA and by a co-treatment with an AMPK inhibitor. These results suggest that emodin isolated from P. multiflorum can be used as a natural anti-neuroinflammatory agent that exerts its effects by inducing HO-1 and NQO1 via AMPK/Nrf2 signaling in microglia.

Emotional arousal and multiple memory systems in the mammalian brain

PubMed Central

Packard, Mark G.; Goodman, Jarid

2012-01-01

Emotional arousal induced by stress and/or anxiety can exert complex effects on learning and memory processes in mammals. Recent studies have begun to link study of the influence of emotional arousal on memory with earlier research indicating that memory is organized in multiple systems in the brain that differ in terms of the “type” of memory they mediate. Specifically, these studies have examined whether emotional arousal may have a differential effect on the “cognitive” and stimulus-response “habit” memory processes sub-served by the hippocampus and dorsal striatum, respectively. Evidence indicates that stress or the peripheral injection of anxiogenic drugs can bias animals and humans toward the use of striatal-dependent habit memory in dual-solution tasks in which both hippocampal and striatal-based strategies can provide an adequate solution. A bias toward the use of habit memory can also be produced by intra-basolateral amygdala (BLA) administration of anxiogenic drugs, consistent with the well documented role of efferent projections of this brain region in mediating the modulatory influence of emotional arousal on memory. In some learning situations, the bias toward the use of habit memory produced by emotional arousal appears to result from an impairing effect on hippocampus-dependent cognitive memory. Further research examining the neural mechanisms linking emotion and the relative use of multiple memory systems should prove useful in view of the potential role for maladaptive habitual behaviors in various human psychopathologies. PMID:22470324

Biocrust-forming mosses mitigate the negative impacts of increasing aridity on ecosystem multifunctionality in drylands.

PubMed

Delgado-Baquerizo, Manuel; Maestre, Fernando T; Eldridge, David J; Bowker, Matthew A; Ochoa, Victoria; Gozalo, Beatriz; Berdugo, Miguel; Val, James; Singh, Brajesh K

2016-03-01

The increase in aridity predicted with climate change will have a negative impact on the multiple functions and services (multifunctionality) provided by dryland ecosystems worldwide. In these ecosystems, soil communities dominated by mosses, lichens and cyanobacteria (biocrusts) play a key role in supporting multifunctionality. However, whether biocrusts can buffer the negative impacts of aridity on important biogeochemical processes controlling carbon (C), nitrogen (N), and phosphorus (P) pools and fluxes remains largely unknown. Here, we conducted an empirical study, using samples from three continents (North America, Europe and Australia), to evaluate how the increase in aridity predicted by climate change will alter the capacity of biocrust-forming mosses to modulate multiple ecosystem processes related to C, N and P cycles. Compared with soil surfaces lacking biocrusts, biocrust-forming mosses enhanced multiple functions related to C, N and P cycling and storage in semiarid and arid, but not in humid and dry-subhumid, environments. Most importantly, we found that the relative positive effects of biocrust-forming mosses on multifunctionality compared with bare soil increased with increasing aridity. These results were mediated by plant cover and the positive effects exerted by biocrust-forming mosses on the abundance of soil bacteria and fungi. Our findings provide strong evidence that the maintenance of biocrusts is crucial to buffer negative effects of climate change on multifunctionality in global drylands. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Piracetam inhibits ethanol (EtOH)-induced memory deficit by mediating multiple pathways.

PubMed

Yang, Yifan; Feng, Jian; Xu, Fangyuan; Wang, Jianglin

2017-12-01

Excessive ethanol (EtOH) intake, especially to prenatal exposure, can significantly affect cognitive function and cause permanent learning and memory injures in children. As a result, how to protect children from EtOH neurotoxicity has gained increasing attention in recent years. Piracetam (Pir) is a nootropic drug derived from c-aminobutyric acid and can manage cognition impairments in multiple neurological disorders. Studies have shown that Pir can exert therapeutic effects on EtOH-induced memory impairments, but the underlying mechanism is still unknown. In this study, we found that Pir inhibited ethanol-induced memory deficit by mediating multiple pathways. Treatment with EtOH could cause cognitive deficit in juvenile rats, and triggered the alteration of synaptic plasticity. Administration with Pir significantly increased long-term potentiation and protected hippocampus neurons from EtOH neurotoxicity. Pir intervention ameliorated EtOH-induced cell apoptosis and inhibited the activation of Caspase-3 in vitro, suggesting that Pir protected neurons by anti-apoptotic effects. Pir could decrease the expression of LC3-II and Beclin-1 induced by EtOH, and increase the phosphorylation of mTOR and reduce the phosphorylation of Akt, which suggested that the protective effect of Pir was involved in regulation of autophagic process and mTOR/Akt pathways. In conclusion, we speculate that Pir reduces EtOH-induced neuronal damage by regulation of apoptotic action and autophagic action, and our research offers preclinical evidence for the application of Pir in ethanol toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Plant volatiles in a polluted atmosphere: stress response and signal degradation

PubMed Central

Blande, James D.; Holopainen, Jarmo K.; Niinemets, Ülo

2014-01-01

Plants emit a plethora of volatile organic compounds, which provide detailed information on the physiological condition of emitters. Volatiles induced by herbivore-feeding are among the best studied plant responses to stress and may constitute an informative message to the surrounding community and function in the process of plant defence. However, under natural conditions, plants are potentially exposed to multiple concurrent stresses, which can have complex effects on the volatile emissions. Atmospheric pollutants are an important facet of the abiotic environment and can impinge on a plant’s volatile-mediated defences in multiple ways at multiple temporal scales. They can exert changes in volatile emissions through oxidative stress, as is the case with ozone pollution. They may also react with volatiles in the atmosphere; such is the case for ozone, nitrogen oxides, hydroxyl radicals and other oxidizing atmospheric species. These reactions result in breakdown products, which may themselves be perceived by community members as informative signals. In this review we demonstrate the complex interplay between stress, emitted signals and modification in signal strength and composition by the atmosphere, collectively determining the responses of the biotic community to elicited signals. PMID:24738697

Immunomodulatory effects of endogenous and synthetic peptides activating opioid receptors.

PubMed

Pomorska, Dorota K; Gach, Katarzyna; Janecka, Anna

2014-01-01

The main role of endogenous opioid peptides is the modulation of pain. Opioid peptides exert their analgesic activity by binding to the opioid receptors distributed widely in the central nervous system (CNS). However, opioid receptors are also found on tissues and organs outside the CNS, including the cells of the immune system, indicating that opioids are capable of exerting additional effects in periphery. Morphine, which is a gold standard in the treatment of chronic pain, is well-known for its immunosuppressive effects. Much less is known about the immunomodulatory effects exerted by endogenous (enkephalins, endorphins, dynorphins and endomorphins) and synthetic peptides activating opioid receptors. In this review we tried to summarize opioid peptide-mediated modulation of immune cell functions which can be stimulatory as well as inhibitory.

Exertional heat illness: emerging concepts and advances in prehospital care.

PubMed

Pryor, Riana R; Roth, Ronald N; Suyama, Joe; Hostler, David

2015-06-01

Exertional heat illness is a classification of disease with clinical presentations that are not always diagnosed easily. Exertional heat stroke is a significant cause of death in competitive sports, and the increasing popularity of marathons races and ultra-endurance competitions will make treating many heat illnesses more common for Emergency Medical Services (EMS) providers. Although evidence is available primarily from case series and healthy volunteer studies, the consensus for treating exertional heat illness, coupled with altered mental status, is whole body rapid cooling. Cold or ice water immersion remains the most effective treatment to achieve this goal. External thermometry is unreliable in the context of heat stress and direct internal temperature measurement by rectal or esophageal probes must be used when diagnosing heat illness and during cooling. With rapid recognition and implementation of effective cooling, most patients suffering from exertional heat stroke will recover quickly and can be discharged home with instructions to rest and to avoid heat stress and exercise for a minimum of 48 hours; although, further research pertaining to return to activity is warranted.

Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects.

PubMed

Bekerman, Elena; Neveu, Gregory; Shulla, Ana; Brannan, Jennifer; Pu, Szu-Yuan; Wang, Stanley; Xiao, Fei; Barouch-Bentov, Rina; Bakken, Russell R; Mateo, Roberto; Govero, Jennifer; Nagamine, Claude M; Diamond, Michael S; De Jonghe, Steven; Herdewijn, Piet; Dye, John M; Randall, Glenn; Einav, Shirit

2017-04-03

Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells. Moreover, we found that multiple viruses, including dengue and Ebola, exploit AAK1 and GAK during entry and infectious virus production. In cultured cells, treatment with sunitinib and erlotinib, approved anticancer drugs that inhibit AAK1 or GAK activity, or with more selective compounds inhibited intracellular trafficking of HCV and multiple unrelated RNA viruses with a high barrier to resistance. In murine models of dengue and Ebola infection, sunitinib/erlotinib combination protected against morbidity and mortality. We validated sunitinib- and erlotinib-mediated inhibition of AAK1 and GAK activity as an important mechanism of antiviral action. Additionally, we revealed potential roles for additional kinase targets. These findings advance our understanding of virus-host interactions and establish a proof of principle for a repurposed, host-targeted approach to combat emerging viruses.

Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects

PubMed Central

Bekerman, Elena; Shulla, Ana; Brannan, Jennifer; Wang, Stanley; Barouch-Bentov, Rina; Bakken, Russell R.; Mateo, Roberto; Govero, Jennifer; Nagamine, Claude M.; Diamond, Michael S.; De Jonghe, Steven; Herdewijn, Piet; Dye, John M.; Randall, Glenn

2017-01-01

Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells. Moreover, we found that multiple viruses, including dengue and Ebola, exploit AAK1 and GAK during entry and infectious virus production. In cultured cells, treatment with sunitinib and erlotinib, approved anticancer drugs that inhibit AAK1 or GAK activity, or with more selective compounds inhibited intracellular trafficking of HCV and multiple unrelated RNA viruses with a high barrier to resistance. In murine models of dengue and Ebola infection, sunitinib/erlotinib combination protected against morbidity and mortality. We validated sunitinib- and erlotinib-mediated inhibition of AAK1 and GAK activity as an important mechanism of antiviral action. Additionally, we revealed potential roles for additional kinase targets. These findings advance our understanding of virus-host interactions and establish a proof of principle for a repurposed, host-targeted approach to combat emerging viruses. PMID:28240606

Pre- and Perinatal Risk for Attention-Deficit Hyperactivity Disorder: Does Neuropsychological Weakness Explain the Link?

PubMed

Wiggs, Kelsey; Elmore, Alexis L; Nigg, Joel T; Nikolas, Molly A

2016-11-01

Etiological investigations of attention-deficit hyperactivity disorder (ADHD) and disruptive behavior problems support multiple causal pathways, including involvement of pre- and perinatal risk factors. Because these risks occur early in life, well before observable ADHD and externalizing symptoms emerge, the relation between risk and symptoms may be mediated by neurodevelopmental effects that manifest later in neuropsychological functioning. However, potential dissociable effects of pre/perinatal risk elements on ADHD and familial confounds must also be considered to test alternative hypotheses. 498 youth aged 6-17 years (55.0 % male) completed a multi-stage, multi-informant assessment including parent and teacher symptom reports of symptoms and parent ratings of pre/perinatal health risk indicators. Youth completed a neuropsychological testing battery. Multiple mediation models examined direct effects of pre- and perinatal health risk on ADHD and other disruptive behavior disorder symptoms and indirect effects via neuropsychological functioning. Parental ADHD symptoms and externalizing status was covaried to control for potential familial effects. Effects of prenatal substance exposure on inattention were mediated by memory span and temporal processing deficits. Further, effects of perinatal health risk on inattention, hyperactivity-impulsivity, and ODD were mediated by deficits in response variability and temporal processing. Further, maternal health risks during pregnancy appeared to exert direct rather than indirect effects on outcomes. Results suggest that after controlling for familial relatedness of ADHD between parent and child, early developmental health risks may influence ADHD via effects on neuropsychological processes underpinning the disorder.

Targeting multiple opioid receptors - improved analgesics with reduced side effects?

PubMed

Günther, Thomas; Dasgupta, Pooja; Mann, Anika; Miess, Elke; Kliewer, Andrea; Fritzwanker, Sebastian; Steinborn, Ralph; Schulz, Stefan

2017-04-05

Classical opioid analgesics, including morphine, mediate all of their desired and undesired effects by specific activation of the μ-opioid receptor (μ receptor). The use of morphine for treating chronic pain, however, is limited by the development of constipation, respiratory depression, tolerance and dependence. Analgesic effects can also be mediated through other members of the opioid receptor family such as the κ-opioid receptor (κ receptor), δ-opioid receptor (δ receptor) and the nociceptin/orphanin FQ peptide receptor (NOP receptor). Currently, a new generation of opioid analgesics is being developed that can simultaneously bind with high affinity to multiple opioid receptors. With this new action profile, it is hoped that additional analgesic effects and fewer side effects can be achieved. Recent research is mainly focused on the development of bifunctional μ/NOP receptor agonists, which has already led to novel lead structures such as the spiroindole-based cebranopadol and a compound class with a piperidin-4-yl-1,3-dihydroindol-2-one backbone (SR16835/AT-202 and SR14150/AT-200). In addition, the ornivol BU08028 is an analogue of the clinically well-established buprenorphine. Moreover, the morphinan-based nalfurafine exerts its effect with a dominant κ receptor-component and is therefore utilized in the treatment of pruritus. The very potent dihydroetorphine is a true multi-receptor opioid ligand in that it binds to μ, κ and δ receptors. The main focus of this review is to assess the paradigm of opioid ligands targeting multiple receptors with a single chemical entity. We reflect on this rationale by discussing the biological actions of particular multi-opioid receptor ligands, but not on their medicinal chemistry and design. © 2017 The British Pharmacological Society.

Influence of ambient music on perceived exertion during a pulmonary rehabilitation session: a randomized crossover study.

PubMed

Reychler, Gregory; Mottart, Florian; Boland, Maelle; Wasterlain, Emmanuelle; Pieters, Thierry; Caty, Gilles; Liistro, Giuseppe

2015-05-01

Pulmonary rehabilitation is a key element in the treatment of COPD. Music has been shown to have a positive effect on parameters related to a decrease in exercise tolerance. The aim of this study was to evaluate the effect of listening to ambient music on perceived exertion during a pulmonary rehabilitation session for COPD subjects. COPD subjects randomly performed a session of pulmonary rehabilitation with or without ambient music. Perceived exertion (Borg scales), anxiety (Hospital Anxiety and Depression Scale-Anxiety Subscale), dyspnea (visual analog scale), and cardiorespiratory parameters were compared at the end of both sessions. Forty-one subjects were analyzed. The characteristics of the COPD subjects were as follows: age, 70.5 ± 8.4 y; body mass index, 22.7 ± 3.9 kg/m(2); and FEV1, 38.6 ± 12.5 % predicted. Perceived exertion was not modified by ambient music, but anxiety was improved (P = .02). Dyspnea, fatigue and cardiorespiratory parameters were not influenced by music during a typical session of the pulmonary rehabilitation program. This study demonstrates that perceived exertion during one pulmonary rehabilitation session was not influenced by ambient music. However, a positive effect on anxiety was observed. (ClinicalTrials.gov registration NCT01833260.). Copyright © 2015 by Daedalus Enterprises.

The effect of bracing availability on one-hand isometric force exertion capability.

PubMed

Jones, Monica L H; Reed, Matthew P; Chaffin, Don B

2013-01-01

Environmental obstructions that workers encounter can kinematically limit the postures that they can achieve. However, such obstructions can also provide an opportunity for additional support by bracing with the hand, thigh or other body part. The reaction forces on bracing surfaces, which are in addition to those acting at the feet and task hand, are hypothesised to improve force exertion capability, and become required inputs to biomechanical analysis of tasks with bracing. The effects of kinematic constraints and associated bracing opportunities on isometric hand force were quantified in a laboratory study of 22 men and women. Analyses of one-hand maximal push, pull and lift tasks demonstrated that bracing surfaces available at the thighs and non-task hand enabled participants to exert an average of 43% more force at the task hand. Task hand force direction deviated significantly from the nominal direction for exertions performed with bracing at both medium and low task hand locations. This study quantifies the effect of bracing on kinematically constrained force exertions. Knowledge that appropriate bracing surfaces can substantially increase hand force is critical to the evaluation of task-oriented strength capability. Force estimates may also involve large off-axis components, which have clear implications for ergonomic analyses of manual tasks.

[Characteristics of elderly heat illness patients in Japan--analysis from Heatstroke STUDY 2010].

PubMed

Miyake, Yasufumi

2013-06-01

Heatstroke Surveillance Committee of the Japanese Association for Acute Medicine (JAAM) collected the clinical data of 1,775 heat illness patients transported into 94 Emergency Medical Centers or Emergency Departments throughout Japan from 1 July to 31 August 2010 (Heatstroke STUDY 2010). Seven hundreds and four elderly patients' data revealed that 541 cases (80%) suffered from classical heatstroke in the ordinary life and the morbidity and mortality were much higher than those of exertional heatstroke patients. Hypertension, diabetes, heart disease and dementia were the risk factors of this disease. Forty nine patients (6.9%) were the victims of classical heatstroke and multiple organ failure include heart failure was the major cause of heat related death in acute phase after admission. No one died in exertional heatstroke group.

The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros and MYC signaling

PubMed Central

Díaz, Tania; Rodríguez, Vanina; Lozano, Ester; Mena, Mari-Pau; Calderón, Marcos; Rosiñol, Laura; Martínez, Antonio; Tovar, Natalia; Pérez-Galán, Patricia; Bladé, Joan; Roué, Gaël; de Larrea, Carlos Fernández

2017-01-01

Most patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequent reduction in IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinational effect of an MYC-interfering therapy with lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the combination of the BET bromodomain inhibitor CPI203 with the lenalidomide/dexamethasone regimen in myeloma cell lines. CPI203 exerted a dose-dependent cell growth inhibition in cell lines, indeed in lenalidomide/dexamethasone-resistant cells (median response at 0.5 μM: 65.4%), characterized by G1 cell cycle blockade and a concomitant inhibition of MYC and Ikaros signaling. These effects were potentiated by the addition of lenalidomide/dexamethasone. Results were validated in primary plasma cells from patients with multiple myeloma co-cultured with the mesenchymal stromal cell line stromaNKtert. Consistently, the drug combination evoked a 50% reduction in cell proliferation and correlated with basal Ikaros mRNA expression levels (P=0.04). Finally, in a SCID mouse xenotransplant model of myeloma, addition of CPI203 to lenalidomide/dexamethasone decreased tumor burden, evidenced by a lower glucose uptake and increase in the growth arrest marker GADD45B, with simultaneous downregulation of key transcription factors such as MYC, Ikaros and IRF4. Taken together, our data show that the combination of a BET bromodomain inhibitor with a lenalidomide-based regimen may represent a therapeutic approach to improve the response in relapsed/refractory patients with multiple myeloma, even in cases with suboptimal prior response to immunomodulatory drugs. PMID:28751557

Estrogen receptors in neuropeptide Y neurons: at the crossroads of feeding and reproduction.

PubMed

Acosta-Martinez, Maricedes; Horton, Teresa; Levine, Jon E

2007-03-01

Hypothalamic neuropeptide Y (NPY) neurons function as physiological integrators in at least two different neuroendocrine systems - one governing feeding and the other controlling reproduction. Estrogen might modulate both systems by regulating NPY gene expression; it might reduce food intake by suppressing NPY expression, and evoke reproductive hormone surges by stimulating it. How can estrogen exert opposing effects in an ostensibly homogeneous NPY neuronal population? Recent work with immortalized NPY-producing cells suggests that the ratio of estrogen receptor alpha:estrogen receptor beta can determine the direction and temporal pattern of transcriptional responses to estrogen. Because this ratio might itself be physiologically regulated, these findings provide one explanation for multiple neuropeptidergic responses to a single steroid hormone.

Neutral Theory and Rapidly Evolving Viral Pathogens.

PubMed

Frost, Simon D W; Magalis, Brittany Rife; Kosakovsky Pond, Sergei L

2018-06-01

The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.

Neuromuscular complications of thyrotoxicosis.

PubMed

Kung, Annie W C

2007-11-01

Thyroid hormones exert multiple effects on the neuromuscular system and the brain, with the most important being their role in stimulating the development and differentiation of the neuromuscular system and brain in foetal and neonatal life. In the presence of hyperthyroidism, muscular and neurological symptoms may be the presenting clinical features of the disease. The frequency and severity of neuromuscular complications vary considerably and are probably related to the degree of hyperthyroidism, although in some patients the neuromuscular dysfunction is caused by associated disorders rather than by hyperthyroidism per se. This update focuses on the most common neurological and muscular disorders that occur in patients with thyrotoxicosis. It is beyond the scope of this paper to discuss thyroid eye disease and cardiac complications, in themselves separate complications of specific myocytes.

Progressive exercise preconditioning protects against circulatory shock during experimental heatstroke.

PubMed

Hung, Ching-Hsia; Chang, Nen-Chung; Cheng, Bor-Chih; Lin, Mao-Tsun

2005-05-01

Heat shock protein (HSP) 72 expression protects against arterial hypotension in rat heatstroke. HSP72 can also be induced in multiple organs, including hearts from rats with endurance exercise. We validated the hypothesis that progressive exercise preconditioning may confer cardiovascular protection during heatstroke by inducing the overexpression of HSP72 in multiple organs. To deal with the matter, we assessed the effects of heatstroke on mean arterial pressure, heart rate, cardiac output, stroke volume, total peripheral vascular resistance, colonic temperature, blood gases, and serum or tissue levels of tumor necrosis factor-alpha (TNF-alpha) in urethane-anesthetized rats pretreated without or with progressive exercise training for 1, 2, or 3 weeks. In addition, HSP72 expression in multiple organs was determined in different groups of animals. Heatstroke was induced by exposing the rats to a high blanket temperature (43 degrees C); the moment at which mean arterial pressure decreased from the peak value was taken as the time of heatstroke onset. Previous exercise training for 3 weeks, but not 1 or 2 weeks, conferred significant protection against hyperthermia, arterial hypotension, decreased cardiac output, decreased stroke volume, decreased peripheral vascular resistance, and increased levels of serum or tissue TNF-alpha during heatstroke and correlated with overexpression of HSP72 in multiple organs, including heart, liver, and adrenal gland. However, 10 days after 3 weeks of progressive exercise training, when HSP72 expression in multiple organs returned to basal values, the beneficial effects exerted by 3 weeks of exercise training were no longer observed. These results strongly suggest that HSP72 preconditioning with progressive exercise training protects against hyperthermia, circulatory shock, and TNF-alpha overproduction during heatstroke.

An unusual presentation of papillary fibroelastoma originating from right ventricular outflow tract.

PubMed

Erdogan, Mehmet; Guney, Murat Can; Ayhan, Hüseyin; Kasapkara, Hacı Ahmet; Uğuz, Emrah; Durmaz, Tahir; Keleş, Telat; Bozkurt, Engin

2017-03-01

Papillary fibroelastomas (PFEs) are primary cardiac tumors with a benign and avascular nature. Majority of the PFEs are originated from the valvular endocardium, while the most common site is aortic valve. In this case, we present a patient with multiple PFEs originating from the right ventricular outflow tract who was admitted to our clinic with exertional dyspnea. As far as we know, this is the first case of this unusual presentation of multiple PFEs and also had a history of breast cancer and permanent pacemaker reported in the literature. © 2017, Wiley Periodicals, Inc.

Cholinergic and serotonergic modulation of visual information processing in monkey V1.

PubMed

Shimegi, Satoshi; Kimura, Akihiro; Sato, Akinori; Aoyama, Chisa; Mizuyama, Ryo; Tsunoda, Keisuke; Ueda, Fuyuki; Araki, Sera; Goya, Ryoma; Sato, Hiromichi

2016-09-01

The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular level, cholinergic/monoaminergic transmitters have been extensively studied as key players for the state/context-dependent modulation of brain function. In this paper, we review how cortical visual information processing in the primary visual cortex (V1) of macaque monkey, which has a highly differentiated laminar structure, is optimized by serotonergic and cholinergic systems by examining anatomical and in vivo electrophysiological aspects to highlight their similarities and distinctions. We show that these two systems have a similar layer bias for axonal fiber innervation and receptor distribution. The common target sites are the geniculorecipient layers and geniculocortical fibers, where the appropriate gain control is established through a geniculocortical signal transformation. Both systems exert activity-dependent response gain control across layers, but in a manner consistent with the receptor subtype. The serotonergic receptors 5-HT1B and 5HT2A modulate the contrast-response curve in a manner consistent with bi-directional response gain control, where the sign (facilitation/suppression) is switched according to the firing rate and is complementary to the other. On the other hand, cholinergic nicotinic/muscarinic receptors exert mono-directional response gain control without a sign reversal. Nicotinic receptors increase the response magnitude in a multiplicative manner, while muscarinic receptors exert both suppressive and facilitative effects. We discuss the implications of the two neuromodulator systems in hierarchical visual signal processing in V1 on the basis of the developed laminar structure. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Serum Tumor Necrosis Factor-alpha associates with Myocardial Oxygen Demand and Exercise Tolerance in Postmenopausal Women.

PubMed

Carter, Stephen J; Bryan, David R; Neumeier, William H; Glasser, Stephen P; Hunter, Gary R

2018-01-01

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO 2max ). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest and during two submaximal workloads (i.e., ≈55% and ≈75% VO 2max ). RPP was calculated by dividing the product of heart rate and systolic blood pressure (via auscultation) by 100. Exercise tolerance corresponded with the cessation of the graded exercise test. During higher-intensity exertion, ≈75% VO 2max , multiple linear regression revealed a positive association ( r = 0.43; p = 0.015) between TNF-α and RPP while adjusting for maximal heart rate, VO 2max , large artery compliance, and percent body fat. Path analyses revealed a significant indirect effect of large artery compliance on exercise tolerance through TNF-α, β = 0.13, CI [0.03, 0.35], indicating greater levels of TNF-α associated with poorer exercise tolerance. These data suggest TNF-α independently associates with myocardial oxygen demand during physical exertion, thus highlighting the utility of higher-intensity efforts to expose important phenomena not apparent at rest. TNF-α also appears to be indirectly associated with the link between large artery compliance and exercise tolerance.

Identification and Quantification of Cumulative Factors that ...

EPA Pesticide Factsheets

Evaluating the combined adverse effects of multiple stressors upon human health is an imperative component of cumulative risk assessment (CRA)1. In addition to chemical stressors, other non-chemical factors are also considered. For examples, smoking will elevate the risks of having lung cancer associated with radon exposure2; toluene and noise together will induce higher levels of hearing loss3; children exposed to violence will have higher risks of developing asthma in the presence of air pollution4. Environmental Justice (EJ) indicators, used as a tool to assess and quantify some of these non-chemical factors, include health, economic, and social indicators such as vulnerability and susceptibility5. Vulnerability factors encompass race, ethnicity, behavior, geographic location, etc., while susceptibility factors include life stage, genetic predisposition, pre-existing health condition and others6, although these two categories are not always mutually exclusive. Numerous findings regarding combined effects of EJ indicators and chemical stressors have been identified7-11. However, fewer studies have analyzed the interrelation between multiple stressors that exert combined harmful effects upon individual or population health in the context of exposure assessment within the risk assessment framework12. In this study, we connected EJ indicators to variables in the exposure assessment model, especially the Average Daily Dose (ADD) model13, in order to better underst

Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

PubMed Central

Al-Habib, Mey; Yu, Zongdong

2013-01-01

One fundamental issue regarding stem cells for regenerative medicine is the maintenance of stem cell stemness. The purpose of the study was to test whether small molecules can enhance stem cell properties of mesenchymal stem cells (MSCs) derived from human dental pulp (hDPSCs), which have potential for multiple clinical applications. We identified the effects of small molecules (Pluripotin (SC1), 6-bromoindirubin-3-oxime and rapamycin) on the maintenance of hDPSC properties in vitro and the mechanisms involved in exerting the effects. Primary cultures of hDPSCs were exposed to optimal concentrations of these small molecules. Treated hDPSCs were analyzed for their proliferation, the expression levels of pluripotent and MSC markers, differentiation capacities, and intracellular signaling activations. We found that small molecule treatments decreased cell proliferation and increased the expression of STRO-1, NANOG, OCT4, and SOX2, while diminishing cell differentiation into odonto/osteogenic, adipogenic, and neurogenic lineages in vitro. These effects involved Ras-GAP-, ERK1/2-, and mTOR-signaling pathways, which may preserve the cell self-renewal capacity, while suppressing differentiation. We conclude that small molecules appear to enhance the immature state of hDPSCs in culture, which may be used as a strategy for adult stem cell maintenance and extend their capacity for regenerative applications. PMID:23573877

Ept7 influences estrogen action in the pituitary gland and body weight of rats.

PubMed

Kurz, Scott G; Dennison, Kirsten L; Samanas, Nyssa Becker; Hickman, Maureen Peters; Eckert, Quincy A; Walker, Tiffany L; Cupp, Andrea S; Shull, James D

2014-06-01

Estrogens control many aspects of pituitary gland biology, including regulation of lactotroph homeostasis and synthesis and secretion of prolactin. In rat models, these actions are strain specific and heritable, and multiple quantitative trait loci (QTL) have been mapped that impact the responsiveness of the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female progeny generated in an intercross between BN rats, in which the lactotroph population is insensitive to estrogens, and ACI rats, which develop lactotroph hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen treatment. The primary objective of this study was to confirm the existence of Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary gland of female and male rats to 17β-estradiol (E2) and diethylstilbestrol (DES), respectively. Secondary objectives were to determine if Ept7 influences the responsiveness of the male reproductive tract to DES and to identify other discernible phenotypes influenced by Ept7. To achieve these objectives, a congenic rat strain that harbors BN alleles across the Ept7 interval on the genetic background of the ACI strain was generated and characterized to define the effect of administered estrogens on the anterior pituitary gland and male reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect on development of lactotroph hyperplasia in response to estrogen treatment, but does not affect atrophy of the male reproductive tissues in response to hormone treatment. Ept7 was also observed to exert gender specific effects on body weight in young adult rats.

An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model.

PubMed

Nishimoto, Tetsuya; Mlakar, Logan; Takihara, Takahisa; Feghali-Bostwick, Carol

2015-10-01

Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6-8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) was orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20 μg of oral E4 peptide ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 μg) were insufficient to exert anti-fibrotic activity when given as a single dose. Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at lower doses. E4 peptide shows oral bioavailability and exerts anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest that E4 peptide is a novel oral drug for fibroproliferative disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model

PubMed Central

Nishimoto, Tetsuya; Mlakar, Logan; Takihara, Takahisa; Feghali-Bostwick, Carol

2016-01-01

Objective Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Methods Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6–8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) were orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Results Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20μg of oral E4 peptide ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 μg) were insufficient to exert anti-fibrotic activity when given as a single dose. Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at lower doses. Conclusion E4 peptide shows oral bioavailability and exerts anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest that E4 peptide is a novel oral drug for fibroproliferative disorders. PMID:26315492

[Effect of 2-deoxy-d-glucose on enterovirus reproduction in HEp-2 cell cultures].

PubMed

Shirobokov, V P

1976-01-01

The influence of 2-deoxy-d-glucose (2DG) on reproduction of some enteroviruses was studied. When 2DG was added to carbohydrate-free medium. It exerted a marked inhibiting effect on reproduction of poliovirus type I (virulent and attenuated variants) and Coxsackie B1, B2, B3, B5 and B6 viruses. The agent was inactive for virulent and attenuated poliomyelitis type II viruses. Poliomyelitis type III and Coxsackie B4 viruses were shown to be incable of multiplication in carbohydrate-free medium when the maintenance medium in cell cultures was lactalbumin hydrolysate in Hank's solution without-glucose. The inhibiting effect of 2DG on sensitive enteroviruses was irreversible and manifest at a concentration as low as 0.1 mg/ml. The effect of the agent was directed to the active stages of intracellular enterovirus synthesis. The possible mechanism of inhibition of enterovirus reproduction in the presence of 2DG is discussed.

Protective Effect of Glucosinolates Hydrolytic Products in Neurodegenerative Diseases (NDDs).

PubMed

Jaafaru, Mohammed Sani; Abd Karim, Nurul Ashikin; Enas, Mohamad Eliaser; Rollin, Patrick; Mazzon, Emanuela; Abdull Razis, Ahmad Faizal

2018-05-08

Crucifer vegetables, Brassicaceae and other species of the order Brassicales, e.g., Moringaceae that are commonly consumed as spice and food, have been reported to have potential benefits for the treatment and prevention of several health disorders. Though epidemiologically inconclusive, investigations have shown that consumption of those vegetables may result in reducing and preventing the risks associated with neurodegenerative disease development and may also exert other biological protections in humans. The neuroprotective effects of these vegetables have been ascribed to their secondary metabolites, glucosinolates (GLs), and their related hydrolytic products, isothiocyanates (ITCs) that are largely investigated for their various medicinal effects. Extensive pre-clinical studies have revealed more than a few molecular mechanisms of action elucidating multiple biological effects of GLs hydrolytic products. This review summarizes the most significant and up-to-date in vitro and in vivo neuroprotective actions of sulforaphane (SFN), moringin (MG), phenethyl isothiocyanate (PEITC), 6-(methylsulfinyl) hexyl isothiocyanate (6-MSITC) and erucin (ER) in neurodegenerative diseases.

A role for the mitochondrial pyruvate carrier as a repressor of the Warburg Effect and colon cancer cell growth

PubMed Central

Schell, John C.; Olson, Kristofor A.; Jiang, Lei; Hawkins, Amy J.; Van Vranken, Jonathan G.; Xie, Jianxin; Egnatchik, Robert A.; Earl, Espen G.; Deberardinis, Ralph J.; Rutter, Jared

2014-01-01

Summary Cancer cells are typically subject to profound metabolic alterations, including the Warburg effect wherein cancer cells oxidize a decreased fraction of the pyruvate generated from glycolysis. We show herein that the mitochondrial pyruvate carrier (MPC), composed of the products of the MPC1 and MPC2 genes, modulates fractional pyruvate oxidation. MPC1 is deleted or underexpressed in multiple cancers and correlates with poor prognosis. Cancer cells re-expressing MPC1 and MPC2 display increased mitochondrial pyruvate oxidation, with no changes in cell growth in adherent culture. MPC re-expression exerted profound effects in anchorage-independent growth conditions, however, including impaired colony formation in soft agar, spheroid formation, and xenograft growth. We also observed a decrease in markers of stemness and traced the growth effects of MPC expression to the stem cell compartment. We propose that reduced MPC activity is an important aspect of cancer metabolism, perhaps through altering the maintenance and fate of stem cells. PMID:25458841

Apparent competition and native consumers exacerbate the strong competitive effect of an exotic plant species.

PubMed

Orrock, John L; Dutra, Humberto P; Marquis, Robert J; Barber, Nicholas

2015-04-01

Direct and indirect effects can play a key role in invasions, but experiments evaluating both are rare. We examined the roles of direct competition and apparent competition by exotic Amur honeysuckle (Lonicera maackii) by manipulating (1) L. maackii vegetation, (2) presence of L. maackii fruits, and (3) access to plants by small mammals and deer. Direct competition with L. maackii reduced the abundance and richness of native and exotic species, and native consumers significantly reduced the abundance and richness of native species. Although effects of direct competition and consumption were more pervasive, richness of native plants was also reduced through apparent competition, as small-mammal consumers reduced richness only when L. maackii fruits were present. Our experiment reveals the multiple, interactive pathways that affect the success and impact of an invasive exotic plant: exotic plants may directly benefit from reduced attack by native consumers, may directly exert strong competitive effects on native plants, and may also benefit from apparent competition.

Amino acids as central synaptic transmitters or modulators in mammalian thermoregulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bligh, J.

1981-11-01

Of the amino acids that affect the activity of central neurons, aspartate and glutamate (which exert generally excitatory influences) and glycine, taurine, and ..gamma..-aminobutyric acid (GABA) (which generally exert inhibitory influences) are the strongest neurotransmitter candidates. As with other putative transmitter substances, their effects on body temperature when injected into the cerebral ventricles or the preoptic hypothalamus tend to vary within and between species. These effects are uninterpretable without accompanying information regarding effector activity changes and the influences of dose and ambient temperature. Observations necessary for analysis of apparent action have been made in studies of the effects of intracerebroventricularmore » injections of these amino acids into sheep. Aspartate and glutamate have similar excitatory effects on the pathway from cold sensors, whereas taurine and GABA exert inhibitory influences on the neural pathways that activate both heat production and heat loss effectors. Glycine appears to be without effect.« less

Flavocoxid exerts a potent antiviral effect against hepatitis B virus.

PubMed

Pollicino, Teresa; Musolino, Cristina; Irrera, Natasha; Bitto, Alessandra; Lombardo, Daniele; Timmoneri, Martina; Minutoli, Letteria; Raimondo, Giovanni; Squadrito, Giovanni; Squadrito, Francesco; Altavilla, Domenica

2018-01-01

Flavocoxid is a proprietary blend of two flavonoids, baicalin and catechin, and recent evidence has shown that bioflavonoids may exert antiviral activities. The potential antiviral activity of Flavocoxid against hepatitis B virus (HBV) was evaluated. Additionally, it was investigated if Flavocoxid used in combination with Entecavir could potentiate its anti-HBV activity. Hepatoma cells replicating HBV were treated with Flavocoxid, or Entecavir alone or in combination for up to 5 days. Viral replicative intermediates, transcripts, and cccDNA levels were evaluated in HBV-replicating cells by real-time PCR, Southern and Northern blotting. Expression profiling was performed using TaqMan low-density arrays. Flavocoxid treatment induced a reduction of HBV replicative intermediates, the amount of transcripts, and HBsAg levels. Flavocoxid and Entecavir combination therapy further decreased the amount of HBV replicative intermediates, compared to Flavocoxid alone. Importantly, Flavocoxid alone or in combination with Entecavir also induced a reduction of cccDNA. Gene-expression analysis showed that Flavocoxid activates type I IFNs-signaling and dampens the HBV-induced inflammatory response. Flavocoxid inhibits HBV replication by targeting multiple steps of viral life cycle. These results indicate that the antiviral activity of Entecavir is potentiated by Flavocoxid, suggesting that this medical food might be considered as an adjuvant for anti-HBV therapy.

Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid

PubMed Central

Shaeib, Faten; Khan, Sana N.; Ali, Iyad; Najafi, Tohid; Maitra, Dhiman; Abdulhamid, Ibrahim; Saed, Ghassan M.; Pennathur, Subramaniam; Abu-Soud, Husam M.

2015-01-01

Myeloperoxidase (MPO) generated hypochlorous acid (HOCl) formed during catalysis is able to destroy the MPO heme moiety through a feedback mechanism, resulting in the accumulation of free iron. Here we show that the presence of melatonin (MLT) can prevent HOCl-mediated MPO heme destruction using a combination of UV-visible photometry, hydrogen peroxide (H2O2)-specific electrode, and ferrozine assay techniques. High performance liquid chromatography (HPLC) analysis showed that MPO heme protection was at the expense of MLT oxidation. The full protection of the MPO heme requires the presence of a 1:2 MLT to H2O2 ratio. Melatonin prevents HOCl–mediated MPO heme destruction through multiple pathways. These include competition with chloride, the natural co-substrate; switching the MPO activity from a two electron oxidation to a one electron pathway causing the buildup of the inactive Compound II, and its subsequent decay to MPO-Fe(III) instead of generating HOCl; binding to MPO above the heme iron, thereby preventing the access of H2O2 to the catalytic site of the enzyme; and direct scavenging of HOCl. Collectively, in addition to acting as an antioxidant and MPO inhibitor, MLT can exert its protective effect by preventing the release of free iron mediated by self-generated HOCl. Our work may establish a direct mechanistic link by which MLT exerts its antioxidant protective effect in chronic inflammatory diseases with MPO elevation. PMID:25835505

Glycosylated Chromogranin A: Potential Role in the Pathogenesis of Heart Failure.

PubMed

Ottesen, Anett H; Christensen, Geir; Omland, Torbjørn; Røsjø, Helge

2017-12-01

Endocrine and paracrine factors influence the cardiovascular system and the heart by a number of different mechanisms. The chromogranin-secretogranin (granin) proteins seem to represent a new family of proteins that exerts both direct and indirect effects on cardiac and vascular functions. The granin proteins are produced in multiple tissues, including cardiac cells, and circulating granin protein concentrations provide incremental prognostic information to established risk indices in patients with myocardial dysfunction. In this review, we provide recent data for the granin proteins in relation with cardiovascular disease, and with a special focus on chromogranin A and heart failure. Chromogranin A is the most studied member of the granin protein family, and shorter, functionally active peptide fragments of chromogranin A exert protective effects on myocardial cell death, ischemia-reperfusion injury, and cardiomyocyte Ca 2+ handling. Granin peptides have also been found to induce angiogenesis and vasculogenesis. Protein glycosylation is an important post-translational regulatory mechanism, and we recently found chromogranin A molecules to be hyperglycosylated in the failing myocardium. Chromogranin A hyperglycosylation impaired processing of full-length chromogranin A molecules into physiologically active chromogranin A peptides, and patients with acute heart failure and low rate of chromogranin A processing had increased mortality compared to other acute heart failure patients. Other studies have also demonstrated that circulating granin protein concentrations increase in parallel with heart failure disease stage. The granin protein family seems to influence heart failure pathophysiology, and chromogranin A hyperglycosylation could directly be implicated in heart failure disease progression.

Quantification of the impact of macrophytes on oxygen dynamics and nitrogen retention in a vegetated lowland river

NASA Astrophysics Data System (ADS)

Desmet, N. J. S.; Van Belleghem, S.; Seuntjens, P.; Bouma, T. J.; Buis, K.; Meire, P.

When macrophytes are growing in the river, the vegetation induces substantial changes to the water quality. Some effects are the result of direct interactions, such as photosynthetic activity or nutrient uptake, whereas others may be attributed to indirect effects of the water plants on hydrodynamics and river processes. This research focused on the direct effect of macrophytes on oxygen dynamics and nutrient cycling. Discharge, macrophyte biomass density, basic water quality, dissolved oxygen and nutrient concentrations were in situ monitored throughout the year in a lowland river (Nete catchment, Belgium). In addition, various processes were investigated in more detail in multiple ex situ experiments. The field and aquaria measurement results clearly demonstrated that aquatic plants can exert considerable impact on dissolved oxygen dynamics in a lowland river. When the river was dominated by macrophytes, dissolved oxygen concentrations varied from 5 to 10 mg l -1. Considering nutrient retention, it was shown that the investigated in-stream macrophytes could take up dissolved inorganic nitrogen (DIN) from the water column at rates of 33-50 mg N kgdry matter-1 h. And DIN fluxes towards the vegetation were found to vary from 0.03 to 0.19 g N ha -1 h -1 in spring and summer. Compared to the measured changes in DIN load over the river stretch, it means that about 3-13% of the DIN retention could be attributed to direct nitrogen uptake from the water by macrophytes. Yet, the role of macrophytes in rivers should not be underrated as aquatic vegetation also exerts considerable indirect effects that may have a greater impact than the direct fixation of nutrients into the plant biomass.

Ethanol and Other Short-Chain Alcohols Inhibit NLRP3 Inflammasome Activation through Protein Tyrosine Phosphatase Stimulation

PubMed Central

Hoyt, Laura R.; Ather, Jennifer L.; Randall, Matthew J.; DePuccio, Daniel P.; Landry, Christopher C.; Wewers, Mark D.; Gavrilin, Mikhail A.; Poynter, Matthew E.

2016-01-01

Immunosuppression is a major complication of alcoholism that contributes to increased rates of opportunistic infections and sepsis in alcoholics. The NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18, can be inhibited by ethanol and we sought to better understand the mechanism through which this occurs and whether chemically similar molecules exert comparable effects. We show that ethanol can specifically inhibit activation of the NLRP3 inflammasome, resulting in attenuated IL-1β and caspase-1 cleavage and secretion, as well as diminished ASC speck formation, without affecting potassium efflux, in a mouse macrophage cell line (J774), mouse bone marrow derived dendritic cells, mouse neutrophils, and human PBMCs. The inhibitory effects on the Nlrp3 inflammasome were independent of GABAA receptor activation or NMDA receptor inhibition, but was associated with decreased oxidant production. Ethanol treatment markedly decreased cellular tyrosine phosphorylation, while administration of the tyrosine phosphatase inhibitor sodium orthovanadate prior to ethanol restored tyrosine phosphorylation and IL-1β secretion subsequent to ATP stimulation. Furthermore, sodium orthovanadate-induced phosphorylation of ASC Y144, necessary and sufficient for Nlrp3 inflammasome activation, and secretion of phosphorylated ASC, were inhibited by ethanol. Finally, multiple alcohol-containing organic compounds exerted inhibitory effects on the Nlrp3 inflammasome, whereas 2-methylbutane (isopentane), the analogous alkane of the potent inhibitor isoamyl alcohol (isopentanol), did not. Our results demonstrate that ethanol antagonizes the NLRP3 inflammasome at an apical event in its activation through the stimulation of protein tyrosine phosphatases, an effect shared by other short-chain alcohols. PMID:27421477

Ethanol and Other Short-Chain Alcohols Inhibit NLRP3 Inflammasome Activation through Protein Tyrosine Phosphatase Stimulation.

PubMed

Hoyt, Laura R; Ather, Jennifer L; Randall, Matthew J; DePuccio, Daniel P; Landry, Christopher C; Wewers, Mark D; Gavrilin, Mikhail A; Poynter, Matthew E

2016-08-15

Immunosuppression is a major complication of alcoholism that contributes to increased rates of opportunistic infections and sepsis in alcoholics. The NLRP3 inflammasome, a multiprotein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the proinflammatory cytokines IL-1β and IL-18, can be inhibited by ethanol, and we sought to better understand the mechanism through which this occurs and whether chemically similar molecules exert comparable effects. We show that ethanol can specifically inhibit activation of the NLRP3 inflammasome, resulting in attenuated IL-1β and caspase-1 cleavage and secretion, as well as diminished apoptosis-associated speck-like protein containing a CARD (ASC) speck formation, without affecting potassium efflux, in a mouse macrophage cell line (J774), mouse bone marrow-derived dendritic cells, mouse neutrophils, and human PBMCs. The inhibitory effects on the Nlrp3 inflammasome were independent of γ-aminobutyric acid A receptor activation or N-methyl-d-asparate receptor inhibition but were associated with decreased oxidant production. Ethanol treatment markedly decreased cellular tyrosine phosphorylation, whereas administration of the tyrosine phosphatase inhibitor sodium orthovanadate prior to ethanol restored tyrosine phosphorylation and IL-1β secretion subsequent to ATP stimulation. Furthermore, sodium orthovanadate-induced phosphorylation of ASC Y144, necessary and sufficient for Nlrp3 inflammasome activation, and secretion of phosphorylated ASC were inhibited by ethanol. Finally, multiple alcohol-containing organic compounds exerted inhibitory effects on the Nlrp3 inflammasome, whereas 2-methylbutane (isopentane), the analogous alkane of the potent inhibitor isoamyl alcohol (isopentanol), did not. Our results demonstrate that ethanol antagonizes the NLRP3 inflammasome at an apical event in its activation through the stimulation of protein tyrosine phosphatases, an effect shared by other short-chain alcohols. Copyright © 2016 by The American Association of Immunologists, Inc.

A chitin-binding lectin from Moringa oleifera seeds (WSMoL) impairs the digestive physiology of the Mediterranean flour larvae, Anagasta kuehniella.

PubMed

de Oliveira, Caio Fernando Ramalho; de Moura, Maiara Celine; Napoleão, Thiago Henrique; Paiva, Patrícia Maria Guedes; Coelho, Luana Cassandra Breitenbach Barroso; Macedo, Maria Lígia Rodrigues

2017-10-01

Biotechnological techniques allow the investigation of alternatives to outdated chemical insecticides for crop protection; some investigations have focused on the identification of molecules tailored from nature for this purpose. We, herein, describe the negative effects of water-soluble lectin from Moringa oleifera seeds (WSMoL) on Anagasta kuehniella development. The chitin-binding lectin, WSMoL, impaired the larval weight gain by 50% and affected the activity of the pest's major digestive enzymes. The commitment of the digestive process became evident after controlled digestion studies, where the capacity of protein digestion was compromised by >90%. Upon acute exposure, the lectin was not resistant to digestion; however, chronic ingestion of WSMoL was able to reverse this feature. Thus, we show that resistance to digestion may not be a prerequisite for a lectin's ability to exert negative effects on larval physiology. The mechanism of action of WSMoL involves binding to chitin with possible disruption to the peritrophic membrane, causing disorder between the endo- and ectoperitrophic spaces. Additionally, results suggest that WSMoL may trigger apoptosis in gut cells, leading to the lower enzymatic activity observed in WSMoL-fed larvae. Although assays employing an artificial diet did not demonstrate effects of WSMoL on A. kuehniella mortality, this lectin may hold potential for exerting insecticide effects on other pest insects, as well for use in other experimental approaches, such as WSMoL-expressing plants. Moreover, the use of WSMoL with other biotechnological tools, such as 'pyramid' crops, may represent a strategy for delaying the evolution of pest resistance to transgenic crops, since its multiple site targets could act in synergism with other insecticide compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na

2013-12-01

AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently withoutmore » changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.« less

Promoting effects of serotonin on hematopoiesis: ex vivo expansion of cord blood CD34+ stem/progenitor cells, proliferation of bone marrow stromal cells, and antiapoptosis.

PubMed

Yang, Mo; Li, Karen; Ng, Pak Cheung; Chuen, Carmen Ka Yee; Lau, Tze Kin; Cheng, Yuan Shan; Liu, Yuan Sheng; Li, Chi Kong; Yuen, Patrick Man Pan; James, Anthony Edward; Lee, Shuk Man; Fok, Tai Fai

2007-07-01

Serotonin is a monoamine neurotransmitter that has multiple extraneuronal functions. We previously reported that serotonin exerted mitogenic stimulation on megakaryocytopoiesis mediated by 5-hydroxytryptamine (5-HT)2 receptors. In this study, we investigated effects of serotonin on ex vivo expansion of human cord blood CD34+ cells, bone marrow (BM) stromal cell colony-forming unit-fibroblast (CFU-F) formation, and antiapoptosis of megakaryoblastic M-07e cells. Our results showed that serotonin at 200 nM significantly enhanced the expansion of CD34+ cells to early stem/progenitors (CD34+ cells, colony-forming unit-mixed [CFU-GEMM]) and multilineage committed progenitors (burst-forming unit/colony-forming unit-erythroid [BFU/CFU-E], colony-forming unit-granulocyte macrophage, colony-forming unit-megakaryocyte, CD61+ CD41+ cells). Serotonin also increased nonobese diabetic/severe combined immunodeficient repopulating cells in the expansion culture in terms of human CD45+, CD33+, CD14+ cells, BFU/CFU-E, and CFU-GEMM engraftment in BM of animals 6 weeks post-transplantation. Serotonin alone or in addition to fibroblast growth factor, platelet-derived growth factor, or vascular endothelial growth factor stimulated BM CFU-F formation. In M-07e cells, serotonin exerted antiapoptotic effects (annexin V, caspase-3, and propidium iodide staining) and reduced mitochondria membrane potential damage. The addition of ketanserin, a competitive antagonist of 5-HT2 receptor, nullified the antiapoptotic effects of serotonin. Our data suggest the involvement of serotonin in promoting hematopoietic stem cells and the BM microenvironment. Serotonin could be developed for clinical ex vivo expansion of hematopoietic stem cells for transplantation. Disclosure of potential conflicts of interest is found at the end of this article.

The influence of the playing surface on the exercise intensity of small-sided recreational soccer games.

PubMed

Brito, João; Krustrup, Peter; Rebelo, António

2012-08-01

This study aimed to analyze the influence of the playing surface on movement pattern, physical loading, perceived exertion, and fatigue development during small-sided recreational soccer games. Time-motion, heart rate, blood lactate, and perceived exertion were measured for 16 recreational players aged 22 (range: 19-35) yrs. During 5-a-side soccer games on 3 different field surfaces: sand, artificial turf, and asphalt. Jump and sprint tests were performed prior to and after each game. Total distance covered was higher on asphalt and turf than on sand (3.89±0.04 and 3.73±0.12 vs. 2.59±0.21 km; p<.01), and the number of high-intensity runs was higher on asphalt than on turf (55±3 vs. 43±3; p<.05), but not sand (46±6). Mean heart rate (means±SEM, 160±3 vs. 171±1 b.p.m.) and time>90% HR(max) (20.8±5.1% vs. 44.1±5.0%) were lower (p<.05) on asphalt than on turf, with intermediate values for sand. Blood lactate was lower on asphalt than on sand (2.8±0.3 vs. 4.7±0.6 mmolL(-1); p<.05). Perceived exertion was lower on asphalt than on turf and sand (VAS 0-100: 52±3 vs. 72±3 and 72±3; p<.01). After the game, squat and countermovement jump performances were lower (4.9-8.1%, and 1.9-6.4%, respectively; p<.001) for all field surfaces, but no changes were observed in 5- and 30-m sprint performance. Small-sided recreational soccer games elicit high heart rates, multiple intense actions, and decreased jump performance for all the investigated playing surfaces, suggesting that multiple fitness and health benefits can be achieved through soccer on sand, artificial turf and asphalt. Nonetheless, locomotor activities, heart rate, blood lactate levels, and perceived exertion differ between surfaces. Copyright © 2012 Elsevier B.V. All rights reserved.

Objective assessment of motor fatigue in multiple sclerosis using kinematic gait analysis: a pilot study

PubMed Central

2011-01-01

Background Fatigue is a frequent and serious symptom in patients with Multiple Sclerosis (MS). However, to date there are only few methods for the objective assessment of fatigue. The aim of this study was to develop a method for the objective assessment of motor fatigue using kinematic gait analysis based on treadmill walking and an infrared-guided system. Patients and methods Fourteen patients with clinically definite MS participated in this study. Fatigue was defined according to the Fatigue Scale for Motor and Cognition (FSMC). Patients underwent a physical exertion test involving walking at their pre-determined patient-specific preferred walking speed until they reached complete exhaustion. Gait was recorded using a video camera, a three line-scanning camera system with 11 infrared sensors. Step length, width and height, maximum circumduction with the right and left leg, maximum knee flexion angle of the right and left leg, and trunk sway were measured and compared using paired t-tests (α = 0.005). In addition, variability in these parameters during one-minute intervals was examined. The fatigue index was defined as the number of significant mean and SD changes from the beginning to the end of the exertion test relative to the total number of gait kinematic parameters. Results Clearly, for some patients the mean gait parameters were more affected than the variability of their movements while other patients had smaller differences in mean gait parameters with greater increases in variability. Finally, for other patients gait changes with physical exertion manifested both in changes in mean gait parameters and in altered variability. The variability and fatigue indices correlated significantly with the motoric but not with the cognitive dimension of the FSMC score (R = -0.602 and R = -0.592, respectively; P < 0.026). Conclusions Changes in gait patterns following a physical exertion test in patients with MS suffering from motor fatigue can be measured objectively. These changes in gait patterns can be described using the motor fatigue index and represent an objective measure to assess motor fatigue in MS patients. The results of this study have important implications for the assessments and treatment evaluations of fatigue in MS. PMID:22029427

Convergence at the faces of development workings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borisenko, A.A.

1977-07-01

Since 1963 we have been carrying out investigations in pits of the Pechora coalfield to establish the general laws of roof-floor convergence in the face areas of development workings and their role in gas bursts. We also considered how various methods of working on the seam influence the amount of type of convergence. The observations were made in 20 workings in five pits of Vorkutaugol Group, cut by cutter-loaders and by drilling and blasting at depths between 350 and 600 m; the cross-sectional areas of the workings ranged frm 3.7 to 12.0 m/sup 2/. The aggregated data on daily convergencemore » values was analyzed by the multiple correlation method with the aid of a computer. The aim of the analysis was to elucidate the influence of six factors on the daily convergence values: the depth below the surface, the corrected seam strength, the cross-sectional area of the working, the initial distance from the face to the measurement prop, the daily advance, and the thickness of the seam. The combined correlation coefficient was rather low - 0.49 with a reliability of 9.13. The greatest influence on the convergence values is exerted by the cross-sectional area and by the distance from the face (the partial correlation coefficients being 0.281 and 0.310, respectively), and lesser influences are exerted by the depth below the surface and by the corrected strength of the seam (partial correlationcoefficients 0.164 and 0.178); the influences of seam thickness and daily face advance are very slight. The multiple correlation results indicate that a very great influence is exerted by disregarded factors, among which the most important are undoubtedly the properties of the surrounding rocks.« less

Quantifying Training Loads in Contemporary Dance.

PubMed

Jeffries, Annie C; Wallace, Lee; Coutts, Aaron J

2017-07-01

To describe the training demands of contemporary dance and determine the validity of using the session rating of perceived exertion (sRPE) to monitor exercise intensity and training load in this activity. In addition, the authors examined the contribution of training (ie, accelerometry and heart rate) and non-training-related factors (ie, sleep and wellness) to perceived exertion during dance training. Training load and ActiGraphy for 16 elite amateur contemporary dancers were collected during a 49-d period, using heart-rate monitors, accelerometry, and sRPE. Within-individual correlation analysis was used to determine relationships between sRPE and several other measures of training intensity and load. Stepwise multiple regressions were used to determine a predictive equation to estimate sRPE during dance training. Average weekly training load was 4283 ± 2442 arbitrary units (AU), monotony 2.13 ± 0.92 AU, strain 10677 ± 9438 AU, and average weekly vector magnitude load 1809,707 ± 1015,402 AU. There were large to very large within-individual correlations between training-load sRPE and various other internal and external measures of intensity and load. The stepwise multiple-regression analysis also revealed that 49.7% of the adjusted variance in training-load sRPE was explained by peak heart rate, metabolic equivalents, soreness, motivation, and sleep quality (y = -4.637 + 13.817%HR peak + 0.316 METS + 0.100 soreness + 0.116 motivation - 0.204 sleep quality). The current findings demonstrate the validity of the sRPE method for quantifying training load in dance, that dancers undertake very high training loads, and a combination of training and nontraining factors contribute to perceived exertion in dance training.

Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells

PubMed Central

Jang, Jinsil; Jeong, Soo-Jin; Kwon, Hee-Young; Jung, Ji Hoon; Sohn, Eun Jung; Lee, Hyo-Jung; Kim, Ji-Hyun; Kim, Sun-Hee; Kim, Jin Hyoung; Kim, Sung-Hoon

2013-01-01

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells. PMID:23818927

Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells.

PubMed

Jang, Jinsil; Jeong, Soo-Jin; Kwon, Hee-Young; Jung, Ji Hoon; Sohn, Eun Jung; Lee, Hyo-Jung; Kim, Ji-Hyun; Kim, Sun-Hee; Kim, Jin Hyoung; Kim, Sung-Hoon

2013-01-01

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.

Estrogen, Angiogenesis, Immunity and Cell Metabolism: Solving the Puzzle.

PubMed

Trenti, Annalisa; Tedesco, Serena; Boscaro, Carlotta; Trevisi, Lucia; Bolego, Chiara; Cignarella, Andrea

2018-03-15

Estrogen plays an important role in the regulation of cardiovascular physiology and the immune system by inducing direct effects on multiple cell types including immune and vascular cells. Sex steroid hormones are implicated in cardiovascular protection, including endothelial healing in case of arterial injury and collateral vessel formation in ischemic tissue. Estrogen can exert potent modulation effects at all levels of the innate and adaptive immune systems. Their action is mediated by interaction with classical estrogen receptors (ERs), ERα and ERβ, as well as the more recently identified G-protein coupled receptor 30/G-protein estrogen receptor 1 (GPER1), via both genomic and non-genomic mechanisms. Emerging data from the literature suggest that estrogen deficiency in menopause is associated with an increased potential for an unresolved inflammatory status. In this review, we provide an overview through the puzzle pieces of how 17β-estradiol can influence the cardiovascular and immune systems.

Optical control of GPR40 signalling in pancreatic β-cells.

PubMed

Frank, James Allen; Yushchenko, Dmytro A; Fine, Nicholas H F; Duca, Margherita; Citir, Mevlut; Broichhagen, Johannes; Hodson, David J; Schultz, Carsten; Trauner, Dirk

2017-11-01

Fatty acids activate GPR40 and K + channels to modulate β-cell function. Herein, we describe the design and synthesis of FAAzo-10 , a light-controllable GPR40 agonist based on Gw-9508. FAAzo-10 is a potent GPR40 agonist in the trans -configuration and can be inactivated on isomerization to cis with UV-A light. Irradiation with blue light reverses this effect, allowing FAAzo-10 activity to be cycled ON and OFF with a high degree of spatiotemporal precision. In dissociated primary mouse β-cells, FAAzo-10 also inactivates voltage-activated and ATP-sensitive K + channels, and allows us to control glucose-stimulated Ca 2+ oscillations in whole islets with light. As such, FAAzo-10 is a useful tool to study the complex effects, with high specificity, which FA-derivatives such as Gw-9508 exert at multiple targets in mouse β-cells.

Possible mechanisms of mammalian immunocontraception.

PubMed

Barber, M R; Fayrer-Hosken, R A

2000-03-01

Ecological and conservation programs in ecosystems around the world have experienced varied success in population management. One of the greatest problems is that human expansion has led to the shrinking of wildlife habitat and, as a result, the overpopulation of many different species has occurred. The pressures exerted by the increased number of animals has caused environmental damage. The humane and practical control of these populations has solicited the scientific community to arrive at a safe, effective, and cost-efficient means of population control. Immunocontraception using zona pellucida antigens, specifically porcine zona pellucida (pZP), has become one of the most promising population control tools in the world today, with notable successes in horses and elephants. A conundrum has risen where pZP, a single vaccine, successfully induces an immunocontraceptive effect in multiple species of mammals. This review describes the most current data pertaining to the mammalian zona pellucida and immunocontraception, and from these studies, we suggest several potential mechanisms of immunocontraception.

“Listening” and “talking” to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids

PubMed Central

Watkins, Linda R.; Hutchinson, Mark R.; Milligan, Erin D.; Maier, Steven F.

2008-01-01

It is recently become clear that activated immune cells and immune-like glial cells can dramatically alter neuronal function. By increasing neuronal excitability, these non-neuronal cells are now implicated in the creation and maintenance of pathological pain, such as occurs in response to peripheral nerve injury. Such effects are exerted at multiple sites along the pain pathway, including at peripheral nerves, dorsal root ganglia, and spinal cord. In addition, activated glial cells are now recognized as disrupting the pain suppressive effects of opioid drugs and contributing to opioid tolerance and opioid dependence/withdrawal. While this review focuses on regulation of pain and opioid actions, such immune-neuronal interactions are broad in their implications. Such changes in neuronal function would be expected to occur wherever immune-derived substances come in close contact with neurons. PMID:17706291

Hemichannels in neurodegenerative diseases: is there a link to pathology?

PubMed Central

Bosch, Megan; Kielian, Tammy

2014-01-01

Although originally considered a structural component of gap junctions, connexin hemichannels (HCs) are now recognized as functional entities capable of influencing metabolic gradients within the CNS, allowing direct communication between the intra- and extracellular milieus. Besides connexins, HCs can also be formed by pannexins, which are not capable of gap junction assembly. Both positive and negative effects have been attributed to HC activity in the context of neurodegenerative diseases. For example, HCs can exert neuroprotective effects by promoting the uptake of neurotoxic molecules, whereas chronic HC opening can disrupt molecular gradients leading to cellular dysfunction and death. The latter scenario has been suggested for multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and more recently, lysosomal storage disorders, which are the focus of this perspective. Currently available evidence suggests a complex role for HCs in neurodegenerative disorders, which sets the stage for future studies to determine whether targeting HC action may improve disease outcomes. PMID:25191227

The interplay between bacillus Calmette-Guérin and Treg cells and its role to prevent or cure inflammatory diseases.

PubMed

Lagranderie, Micheline; Guyonvarc'h, Pierre-Marie

2014-06-01

Clinical evidence indicates that Bacillus Calmette-Guérin (BCG) vaccination exerts anti-inflammatory effects in diseases such as asthma, multiple sclerosis or Type 1 diabetes. Although the exact mechanisms for this activity remain debated, the capacity of mycobacteria to induce regulatory T cells (Tregs) in vivo has been widely reported. However, adverse events associated with live BCG prevent its repeated use, especially in immunocompromised individuals. This article reviews the preclinical data showing a potent, systemic and long-term anti-inflammatory effect in animal models of allergic asthma, inflammatory bowel disease and atherosclerosis with a preparation of BCG inactivated by Extended Freeze-Drying (EFD BCG). It also presents the characteristics of EFD BCG-induced Tregs which play a crucial role in the immunomodulation of various inflammatory diseases. Finally, it compares EFD BCG with other approaches based on the therapeutic use of Tregs in humans.

Reproductive hazards in the workplace: what the practitioner needs to know about chemical exposures.

PubMed

Paul, M; Himmelstein, J

1988-06-01

A growing body of scientific evidence implicates occupational chemical exposures in the etiology of human adverse reproductive outcomes. Most reproductive toxins that have been investigated in sufficient detail have been shown to exert multiple effects on and through both men and women. In the face of growing public awareness, it is essential that clinicians develop a knowledgeable and effective approach to patient concerns about reproductive hazards in the workplace. Of vital importance is the accurate characterization of exposure at the worksite. Intervention strategies for worrisome situations include amelioration of worksite exposure or, as a last resort, temporary, compensated job modification or transfer. The clinician can obtain assistance in addressing the problem from several resources, including local regulatory agencies and occupational health clinics. Widespread involvement of knowledgeable health professionals can have a dramatic impact on improving this important contemporary public health problem.

Epigenetic Regulation by Sulforaphane: Opportunities for Breast and Prostate Cancer Chemoprevention.

PubMed

Atwell, Lauren L; Beaver, Laura M; Shannon, Jackilen; Williams, David E; Dashwood, Roderick H; Ho, Emily

2015-04-01

Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that has multiple molecular targets and anti-cancer properties. Researchers have demonstrated several chemopreventive benefits of SFN consumption, such as reductions in tumor growth, increases in cancer cell apoptosis, and disruption of signaling within tumor microenvironments both in vitro and in vivo . Emerging evidence indicates that SFN exerts several of its chemopreventive effects by altering epigenetic mechanisms. This review summarizes evidence of the impact of SFN on epigenetic events and how they relate to the chemopreventive effects of SFN observed in preclinical and clinical studies of breast and prostate cancers. Specific areas of focus include the role of SFN in the regulation of cell cycle, apoptosis, inflammation, antioxidant defense, and cancer cell signaling and their relationships to epigenetic mechanisms. Finally, remaining challenges and research needs for translating mechanistic work with SFN into human studies and clinical intervention trials are discussed.

Identification of selenium-containing proteins in HEK 293 kidney cells using multiple chromatographies, LC-ICPMS and nano-LC-ESIMS.

PubMed

Chitta, Karnakar R; Landero-Figueroa, Julio A; Kodali, Phanichand; Caruso, Joseph A; Merino, Edward J

2013-09-30

Our previous studies using HeLa and HEK 293 cells demonstrated that selenomethionine, SeMet, exerts more of an antagonistic effect on arsenic than other selenium species. These studies attributed the antagonistic effect of SeMet to decreased levels of reactive oxygen species, ROS, changes in protein phosphorylation and possible incorporation of SeMet into proteins. The present study employs a metallomics approach to identify the selenium-containing proteins in HEK 293 cells raised with SeMet. The proteins were screened and separated using two dimensional high performance liquid chromatography (HPLC)-inductively coupled plasma mass spectrometry (ICPMS), size exclusion chromatography (SEC) and reversed-phase chromatography (RPC). The Se-containing proteins were identified by peptide mapping using nano-HPLC-Chip-electrospray ionization mass spectrometry (ESIMS). Copyright © 2013 Elsevier B.V. All rights reserved.

Astaxanthin reduces matrix metalloproteinase expression in human chondrocytes.

PubMed

Chen, Wei-Ping; Xiong, Yan; Shi, Yong-Xiang; Hu, Peng-Fei; Bao, Jia-Peng; Wu, Li-Dong

2014-03-01

Astaxanthin is a red carotenoid pigment which exerts multiple biological activities. However, little is known about the effects of astaxanthin on matrix metalloproteinases (MMPs) in OA. The present study investigated the effects of astaxanthin on MMPs in human chondrocytes. Human chondrocytes were pretreated with astaxanthin at 1, 10 or 50μM, then, cells were stimulated with IL-1β (10ng/ml) for 24h. MMP-1, MMP-3 and MMP-13 were observed. We found that astaxanthin reduced the expression of MMP-1, MMP-3 and MMP-13 as well as the phosphorylation of two mitogen-activated protein kinases (MAPK) (p38 and ERK1/2) in IL-1β-stimulated chondrocytes. Astaxanthin also blocked the IκB-α degradation. These results suggest that astaxanthin may be beneficial in the treatment of OA. Copyright © 2013 Elsevier B.V. All rights reserved.

Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures.

PubMed

Yoshino, Atsushi; Polouliakh, Natalia; Meguro, Akira; Takeuchi, Masaki; Kawagoe, Tatsukata; Mizuki, Nobuhisa

2016-01-01

Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients.

Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by inhibiting TGFB1-dependent epithelial mesenchymal transition.

PubMed

Chen, Hong; Chen, Qun; Jiang, Chun-Ming; Shi, Guang-Yue; Sui, Bo-Wen; Zhang, Wei; Yang, Li-Zhen; Li, Zhu-Ying; Liu, Li; Su, Yu-Ming; Zhao, Wen-Cheng; Sun, Hong-Qiang; Li, Zhen-Zi; Fu, Zhou

2018-03-01

Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell proliferation that damages the body. This malignant cell evolution in a stressful environment closely resembles that of epithelial-mesenchymal transition (EMT). As a popular EMT-inducing factor, TGFβ plays an important role in the progression of multiple diseases. However, the drugs that target TGFB1 are limited. In this study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti-lung fibrosis effect by inhibiting the EMT of lung epithelial cells. In addition, triptolide directly binds to TGFβ and subsequently increase E-cadherin expression and decrease vimentin expression. In in vivo studies, TPL improves the survival state and inhibits lung fibrosis in mice. In summary, this study revealed the potential therapeutic effect of paraquat induced TPL in lung fibrosis by regulating TGFβ-dependent EMT progression. Copyright © 2017 Elsevier B.V. All rights reserved.

Outdoor Ambient Air Pollution and Neurodegenerative Diseases: the Neuroinflammation Hypothesis.

PubMed

Jayaraj, Richard L; Rodriguez, Eric A; Wang, Yi; Block, Michelle L

2017-06-01

Accumulating research indicates that ambient outdoor air pollution impacts the brain and may affect neurodegenerative diseases, yet the potential underlying mechanisms are poorly understood. The neuroinflammation hypothesis holds that elevation of cytokines and reactive oxygen species in the brain mediates the deleterious effects of urban air pollution on the central nervous system (CNS). Studies in human and animal research document that neuroinflammation occurs in response to several inhaled pollutants. Microglia are a prominent source of cytokines and reactive oxygen species in the brain, implicated in the progressive neuron damage in diverse neurodegenerative diseases, and activated by inhaled components of urban air pollution through both direct and indirect pathways. The MAC1-NOX2 pathway has been identified as a mechanism through which microglia respond to different forms of air pollution, suggesting a potential common deleterious pathway. Multiple direct and indirect pathways in response to air pollution exposure likely interact in concert to exert CNS effects.

Transport properties of CNT/oligosilane/CNT heterojunctions

NASA Astrophysics Data System (ADS)

Yu, J.; Zhang, G. L.; Shang, Y.; Wang, K. D.; Zhang, H.; Sun, M.; Liu, B.; Zeng, T.

2013-02-01

Combining the non-equilibrium Green's function formalism with density functional theory, the transport properties of nine CNT/oligosilane/CNT heterojunctions were systematically studied. We have found that the incorporation of oligosilane linkage to the carbon nanotube mouth could significantly tune the transport properties compared with the pure oligosilane and pure CNT. The P- and B-dopings upon the oligosilane moiety could not only enhance the conductivity but also give rise to multiple negative differential resistance behavior for the CNT/oligosilane/CNT heterojunctions. The concentration of heteroatom plays an important role in the transport properties of the CNT/oligosilane/CNT heterojunctions, while the number of the oligosilane linkage exerts little effect on the conductivity. The B-doped CNT/oligosilane/CNT heterojunctions show higher conductivity than those of the P-doped ones. The p-n junction caused by B- and P-codopings exhibits a rectifying effect and the rectification ratio is up to 7.19.

Analysis of G-Protein Coupled Receptor 30 (GPR30) on Endothelial Inflammation.

PubMed

Chakrabarti, Subhadeep; Davidge, Sandra T

2016-01-01

The female sex hormone estrogen (the most common form 17-β-estradiol or E2) is known to have both anti-inflammatory and pro-inflammatory effects. Given the diversity of estrogen responses mediated through its three distinct receptors, namely, estrogen receptor α (ERα), ERβ, and the G-protein coupled receptor 30 (GPR30), it is plausible that different receptors have specific modulatory effects on inflammation in different tissues. We have shown that activation of GPR30 exerted anti-inflammatory effects as demonstrated by significant attenuation of tumor necrosis factor (TNF)-mediated upregulation of adhesion molecules in isolated human umbilical vein endothelial cells. Interestingly, estrogen alone had no such effect and blockade of classical ERs restored the anti-inflammatory effect, suggesting that this effect was dependent on GPR30 and opposed to classical ERs. These findings were further validated by the negation of anti-inflammatory GPR30 effects by classical ER agonists. This chapter focuses on multiple pharmacological options to activate GPR30 and the use of TNF activated endothelial cells as a model system for inflammatory response as assessed by adhesion molecule detection through western blotting.

The effects of reading comprehension and launch site on frequency-predictability interactions during paragraph reading.

PubMed

Whitford, Veronica; Titone, Debra

2014-01-01

We used eye movement measures of paragraph reading to examine whether word frequency and predictability interact during the earliest stages of lexical processing, with a specific focus on whether these effects are modulated by individual differences in reading comprehension or launch site (i.e., saccade length between the prior and currently fixated word--a proxy for the amount of parafoveal word processing). The joint impact of frequency and predictability on reading will elucidate whether these variables additively or multiplicatively affect the earliest stages of lexical access, which, in turn, has implications for computational models of eye movements during reading. Linear mixed effects models revealed additive effects during both early- and late-stage reading, where predictability effects were comparable for low- and high-frequency words. Moreover, less cautious readers (e.g., readers who engaged in skimming, scanning, mindless reading) demonstrated smaller frequency effects than more cautious readers. Taken together, our findings suggest that during extended reading, frequency and predictability exert additive influences on lexical and postlexical processing, and that individual differences in reading comprehension modulate sensitivity to the effects of word frequency.

Effect of aspirin on acute changes in peripheral arterial stiffness and endothelial function following exertional heat stress in firefighters: The factorial group results of the Enhanced Firefighter Rehab Trial.

PubMed

Olafiranye, Oladipupo; Hostler, David; Winger, Daniel G; Wang, Li; Reis, Steven E

2015-06-01

Peripheral arterial stiffness and endothelial function, which are independent predictors of cardiac events, are abnormal in firefighters. We examined the effects of aspirin on peripheral arterial stiffness and endothelial function in firefighters. Fifty-two firefighters were randomized to receive daily 81 mg aspirin or placebo for 14 days before treadmill exercise in thermal protection clothing, and a single dose of 325 mg aspirin or placebo immediately following exertion. Peripheral arterial augmentation index adjusted for a heart rate of 75 (AI75) and reactive hyperemia index (RHI) were determined immediately before, and 30, 60, and 90 minutes after exertion. Low-dose aspirin was associated with lower AI75 (-15.25±9.25 vs -8.08±10.70, p=0.014) but not RHI. On repeated measures analysis, treatment with low-dose aspirin before, but not single-dose aspirin after exertion, was associated with lower AI75 following exertional heat stress (p=0.018). Low-dose aspirin improved peripheral arterial stiffness and wave reflection but not endothelial function in firefighters. © The Author(s) 2015.

Caffeine and theanine exert opposite effects on attention under emotional arousal.

PubMed

Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Taylor, Holly A; Kanarek, Robin B

2017-01-01

Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p < 0.05), theanine accentuated local processing (p < 0.05), and the combination did not differ from placebo. Caffeine reduced flanker conflict difference scores on the Attention Network Test (p < 0.05), theanine increased difference scores (p < 0.05), and the combination did not differ from placebo. Thus, under emotional arousal, caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.

Obesity-related differences in neural correlates of force control.

PubMed

Mehta, Ranjana K; Shortz, Ashley E

2014-01-01

Greater body segment mass due to obesity has shown to impair gross and fine motor functions and reduce balance control. While recent studies suggest that obesity may be linked with altered brain functions involved in fine motor tasks, this association is not well investigated. The purpose of this study was to examine the neural correlates of motor performance in non-obese and obese adults during force control of two upper extremity muscles. Nine non-obese and eight obese young adults performed intermittent handgrip and elbow flexion exertions at 30% of their respective muscle strengths for 4 min. Functional near infrared spectroscopy was employed to measure neural activity in the prefrontal cortex bilaterally, joint steadiness was computed using force fluctuations, and ratings of perceived exertions (RPEs) were obtained to assess perceived effort. Obesity was associated with higher force fluctuations and lower prefrontal cortex activation during handgrip exertions, while RPE scores remained similar across both groups. No obesity-related differences in neural activity, force fluctuation, or RPE scores were observed during elbow flexion exertions. The study is one of the first to examine obesity-related differences on prefrontal cortex activation during force control of the upper extremity musculature. The study findings indicate that the neural correlates of motor activity in the obese may be muscle-specific. Future work is warranted to extend the investigation to monitoring multiple motor-function related cortical regions and examining obesity differences with different task parameters (e.g., longer duration, increased precision demands, larger muscles, etc.).

Legacy of top-down herbivore pressure ricochets back up multiple trophic levels in forest canopies over 30 years

Treesearch

Tim Nuttle; Ellen H. Yerger; Scott H. Stoleson; Todd E. Ristau

2011-01-01

Removal of top-down control on herbivores can result in a trophic cascade where herbivore pressure on plants results in changes in plant communities. These altered plant communities are hypothesized to exert bottom-up control on subsequent herbivory via changes in plant quality or productivity. But it remains untested whether top-down perturbation causes long term...

Designing Clothes and Cars: Second Grade Students Using Multiple Forms of Literacy to Try on and Perform Identity

ERIC Educational Resources Information Center

O'Neil, Kathleen Ellen

2015-01-01

Children of elementary school age are in the process of discovering and establishing their self-identity through talk, gesture, writing, and, especially, the arts. While they can sometimes find room to exert their individuality in their daily classroom assignments, it is more often in the spaces open to social interaction in school in which this…

Massive quantum regions for simulations on bio-nanomaterials: synthetic ferritin nanocages.

PubMed

Torras, Juan; Alemán, Carlos

2018-02-22

QM/MM molecular dynamics simulations on the 4His-ΔC* protein cage have been performed using multiple active zones (up to 86 quantum regions). The regulation and nanocage stability exerted by the divalent transition metal ions in the monomer-to-cage conversion have been understood by comparing high level quantum trajectories obtained using Cu 2+ and Ni 2+ coordination ions.

[PHYSICAL EXERCISE FOR PEOPLE WITH MULTIPLE SCLEROSIS: EFFECTS, RECOMMENDATIONS AND BARRIERS].

PubMed

Barak, Sharon; Hutzler, Yeshayahu; Dubnov-Raz, Gal; Achiron, Anat

2016-06-01

This review summarizes the existing knowledge regarding the effects and recommendations for physical training (PTr) in patients with multiple sclerosis (MS). In addition, perceived benefits and barriers to PTr in this population are reviewed. One of the primary aims of rehabilitation for patients with MS is to increase their levels of activity and independence. PTr is a central component in the rehabilitation process. Nonetheless, the use of PTr in the rehabilitation of patients with MS has been a controversial issue for years. Nowadays, strong evidence exists that aerobic training in individuals with MS has a positive effect on overall physical conditioning, gait speed, fatigue, depression and cognition. Unlike aerobic training, the number of studies that investigated strength training effects in this population is limited. However, the available data show that resistance training also has beneficial effects on MS patients. It is important to note, that PTr has no deleterious effects in MS patients. In the various studies, there was diversity with regard to the duration and the frequency of PTr, while intensity was often poorly described. It is recommended that individuals with MS engage in aerobic training (at 60-80% of maximal heart rate), strength training (1-3 sets of 8-15 repetitions), the range of motion, balance and ambulation exercises. Awareness of the benefits of physical activity and sense of achievement are not sufficient to promote exercise participation in persons with MS. Factors relating to physical exertion, sports facilities availability and self-efficacy play an important role in promoting exercise participation.

Exercise collapse associated with sickle cell trait (ECAST): case report and literature review.

PubMed

Quattrone, Richard D; Eichner, E Randy; Beutler, Anthony; Adams, W Bruce; O'Connor, Francis G

2015-01-01

Sickle cell trait (SCT) has been associated with exertional collapse (ECAST) and exercise-related sudden death in athletes and military warfighters. The mechanisms underlying ECAST remain controversial in the sports medicine community. Multiple case presentations and anecdotal reports postulate the role of extraordinary exercise intensity, but other risk factors including dehydration, heat, previous exertional rhabdomyolysis, genetic cofactors, and dietary supplements have been cited as potential contributors. Others have hypothesized some of the aforementioned factors combining in a "perfect storm" to trigger ECAST with a resultant potentially fatal "metabolic crisis." This case report provides a brief review of SCT as it pertains to exercise in warfighters and athletes, identifies known and postulated risk factors associated with ECAST, and introduces the potential mechanistic role of the "double hit" as a contributor to ECAST.

Effect of Stimulant Medication Use by Children with ADHD on Heart Rate and Perceived Exertion

ERIC Educational Resources Information Center

Mahon, Anthony D.; Woodruff, Megan E.; Horn, Mary P.; Marjerrison, Andrea D.; Cole, Andrew S.

2012-01-01

The effect of stimulant medication use by children with attention deficit/hyperactivity disorder (ADHD) on the rating of perceived exertion (RPE)--heart rate (HR) relationship was examined. Children with ADHD (n = 20; 11.3 [plus or minus] 1.8 yrs) and children without ADHD (n = 25; 11.2 [plus or minus] 2.1 yrs) were studied. Children with ADHD…

Self-selected music-induced reduction of perceived exertion during moderate-intensity exercise does not interfere with post-exercise improvements in inhibitory control.

PubMed

Tanaka, Daichi; Tsukamoto, Hayato; Suga, Tadashi; Takenaka, Saki; Hamaoka, Takafumi; Hashimoto, Takeshi; Isaka, Tadao

2018-05-26

Acute aerobic exercise improves inhibitory control (IC). This improvement is often associated with increases in perceived exertion during exercise. However, listening to music during aerobic exercise mitigates an exercise-induced increase in perceived exertion. Thus, it is hypothesized that such effects of music may interfere with exercise-induced improvements in IC. To test this hypothesis, we examined the effect of music on post-exercise IC improvements that were induced by moderate-intensity exercise. Fifteen healthy young men performed cycle ergometer exercise with music or non-music. The exercise was performed using a moderate-intensity of 60% of VO 2 peak for 30 min. The music condition was performed while listening to self-selected music. The non-music condition involved no music. To evaluate IC, the Stroop task was administered before exercise, immediately after exercise, and during the 30-min post-exercise recovery period. The rate of perceived exertion immediately before moderate-intensity exercise completed was significantly lower in music condition than in non-music condition. The IC significantly improved immediately after exercise and during the post-exercise recovery period compared to before exercise in both music and non-music conditions. The post-exercise IC improvements did not significantly differ between the two conditions. These findings indicate that self-selected music-induced mitigation of the increase in perceived exertion during moderate-intensity exercise dose not interfere with exercise-induced improvements in IC. Therefore, we suggest that listening to music may be a beneficial strategy in mitigating the increase in perceived exertion during aerobic exercise without decreasing the positive effects on IC. Copyright © 2018 Elsevier Inc. All rights reserved.

1,4-Naphthoquinone derivatives potently suppress Candida albicans growth, inhibit formation of hyphae and show no toxicity toward zebrafish embryos.

PubMed

Janeczko, Monika; Kubiński, Konrad; Martyna, Aleksandra; Muzyczka, Angelika; Boguszewska-Czubara, Anna; Czernik, Sławomir; Tokarska-Rodak, Małgorzata; Chwedczuk, Marta; Demchuk, Oleg M; Golczyk, Hieronim; Masłyk, Maciej

2018-04-01

In this study, we applied various assays to find new activities of 1,4-naphthoquinone derivatives for potential anti-Candida albicans applications. These assays determined (a) the antimicrobial effect on growth/cell multiplication in fungal cultures, (b) the effect on formation of hyphae and biofilm, (c) the influence on cell membrane integrity, (d) the effect on cell morphology using atomic force microscopy, and (e) toxicity against zebrafish embryos. We have demonstrated the activity of these compounds against different Candida species and clinical isolates of C. albicans. 1,4-Naphthoquinones significantly affected fungal strains at 8-250 mg l -1 of MIC. Interestingly, at concentrations below MICs, the chemicals showed effectiveness in inhibition of hyphal formation and cell aggregation in Candida. Of note, atomic force microscopy (AFM) analysis revealed an influence of the compounds on cell morphological properties. However, at low concentrations (0.8-31.2 mg l -1 ), it did not exert any evident toxic effects on zebrafish embryos. Our research has evidenced the effectiveness of 1,4-naphthoquinones as potential anti-Candida agents.

What have we learned about GPER function in physiology and disease from knockout mice?

PubMed Central

Prossnitz, Eric R.; Hathaway, Helen J.

2015-01-01

Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and patho-physiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also revealed roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. PMID:26189910

BDNF val66met Polymorphism Affects Aging of Multiple Types of Memory

PubMed Central

Kennedy, Kristen M.; Reese, Elizabeth D.; Horn, Marci M.; Sizemore, April N.; Unni, Asha K.; Meerbrey, Michael E.; Kalich, Allan G.; Rodrigue, Karen M.

2014-01-01

The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age x BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (p < .07) toward poorer associative memory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory – in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). PMID:25264352

Metabolic effects of silibinin in the rat liver.

PubMed

Colturato, Carina Parisoto; Constantin, Rodrigo Polimeni; Maeda, Antônio Sueiti; Constantin, Renato Polimeni; Yamamoto, Nair Seiko; Bracht, Adelar; Ishii-Iwamoto, Emy Luiza; Constantin, Jorgete

2012-01-25

The flavonolignan silibinin, which is a mixture of two diastereoisomers, silybin A and silybin B, is a component of the extract obtained from the fruit and seeds of the variegated milk thistle (Silybum marianum (L.) Gaertn. (Asteraceae)), known as silymarin. Among the therapeutic properties credited to silibinin, its antihyperglycaemic action has been extensively explored. Silibinin is structurally related to the flavonoids quercetin and fisetin, which have been previously demonstrated to be very active on liver metabolic processes related to glycaemic regulation. The aim of the present work was to investigate the effects of silibinin on metabolic pathways responsible for the maintenance of glycaemia, particularly glycogenolysis and gluconeogenesis, in the perfused rat liver. The activities of some key enzymes in these pathways and on parameters of energy metabolism in isolated mitochondria were also examined. At a concentration range of 50-300μM, silibinin inhibited gluconeogenesis in the fasted condition and inhibited glycogenolysis and glycolysis in the fed condition. The mechanisms by which silibinin exerted these actions were multiple and complex. It inhibited the activity of glucose 6-phosphatase, inhibited the pyruvate carrier, and reduced the efficiency of mitochondrial energy transduction. It can also act by reducing the supply of NADH for gluconeogenesis and mitochondria through its pro-oxidative actions. In general, the effects and the potency of silibinin were similar to those of quercetin and fisetin. However, silibinin exerted some distinct effects such as the inhibitory effect on oxygen consumption in the fed condition and a change in the energy status of the perfused livers. It can be concluded that the effects of silibinin on liver glucose metabolism may explain its antihyperglycaemic property. However, this effect was, in part, secondary to impairment in cellular energy metabolism, a finding that should be considered in its therapeutic usage. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Neuroprotective potential of high-dose biotin.

PubMed

McCarty, Mark F; DiNicolantonio, James J

2017-11-01

A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain-permeable phosphodiesterase-5 inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute recovery from exercise in people with multiple sclerosis: an exploratory study on the effect of exercise intensities.

PubMed

Collett, Johnny; Meaney, Andy; Howells, Ken; Dawes, Helen

2017-03-01

Purpose A better understanding of how people with multiple sclerosis (pwMS) recover from exercise may help inform interventions. Methods We explored physiological and perceptual responses following exercise of different intensities, using a crossover exposure-response design, in 14 adults with multiple sclerosis (MS) and 9 controls. A cycling exercise test determined maximum capacity (Wpeak). Participants then performed 20-min exercise sessions relative to Wpeak (random order separated by 7 days): (1) 45% and (2) 60% continuous cycling and (3) 90% intermittent cycling (30 s cycling, 30 s rest). During a 45-min recovery period, tympanic temperature (Temp°C), exertion in breathing (RPEbr) and legs (RPEleg), and cortical excitability (MEParea) were measured. Results Eleven pwMS and eight controls completed the study. Controls performed better on the exercise test (p < 0.05), thus more absolute work during subsequent sessions. PwMS took longer to recover RPEleg with recovery time increasing with intensity (45%-6 min; 60%-15 min; 90%-35 min) and correlating with Temp°C. MEParea was significantly depressed in both groups at 45% and 60% (p < 0.001), in the MS group this also correlated with RPEleg. Conclusions Feelings of leg exertion may persist after exercise in some pwMS, especially at high intensities. This may relate to body temperature and, after continuous exercise, cortical excitability. These results support considering the recovery period post exercise and provide an insight into potential correlates of post-exercise fatigue. Implications for Rehabilitation A better understanding of how pwMS recover following exercise may help inform exercise prescription a long side fatigue management. This study showed that, in pwMS, the time taken to recover from feelings of leg fatigue increased with the intensity of the exercise session rather that total work performed and was related to increase in body temperature. The results of this relatively small study support the need to consider a recovery period after exercise and provide an insight into potential physiological correlates.

Strength capability while kneeling.

PubMed

Haslegrave, C M; Tracy, M F; Corlett, E N

1997-12-01

Work sometimes has to be carried out kneeling, particularly where jobs are performed in confined spaces as is common for miners, aircraft baggage handlers and maintenance workers. In order to assess the risks in performing forceful tasks under such conditions, data is needed on strength capabilities of kneeling subjects. A study was undertaken to measure isometric strength in single-handed exertions for male subjects and to investigate the effects on this of task layout factors (direction of force exertion, reach distance, height of the workpiece and orientation relative to the subject's sagittal plane). The data has been tabulated to show the degree to which strength may be reduced in different situations and analysis of the task factors showed their influence to be complex with direction of exertion and reach distance having the greatest effect. The results also suggest that exertions are weaker when subjects are kneeling on two knees than when kneeling on one knee, although this needs to be confirmed by direct experimental comparison.

Forskolin: genotoxicity assessment in Allium cepa.

PubMed

Mohammed, Khalid Pasha; Aarey, Archana; Tamkeen, Shayesta; Jahan, Parveen

2015-01-01

Forskolin, a diterpene, 7β-acetoxy-8,13-epoxy-1α,6β,9α-trihydroxy-labd-14-en-11-one (C22H34O7) isolated from Coleus forskohlii, exerts multiple physiological effects by stimulating the enzyme adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) concentrations. Forskolin is used in the treatment of hypertension, congestive heart failure, eczema, and other diseases. A cytogenetic assay was performed in Allium cepa to assess possible genotoxic effects of forskolin. Forskolin was tested at concentrations 5-100 μM for exposure periods of 24 or 48 h. Treated samples showed significant reductions in mitotic index (p < 0.05) and increases in the frequency of chromosome aberrations (p < 0.01) at both exposure times. The treated meristems showed chromosome aberrations including sticky metaphases, sticky anaphases, laggard, anaphase bridges, micronuclei, polyploidy, fragments, breaks, and C-mitosis. Forskolin may cause genotoxic effects and further toxicological evaluations should be conducted to ensure its safety. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of ethylene on gene expression in carrot roots

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, S.E.

1984-01-01

To investigate ethylene effects on expression of genetic information, cDNA clones corresponding to ethylene-induced carrot root mRNAs were constructed and isolated. RNA dot blot analysis showed that for the three clones studied peak cytosolic mRNA prevalence occurred at 21 hours of treatment followed thereafter by rapid messenger decay. DNA filter excess hybridization to in vitro synthesized nuclear RNA showed that the ethylene-induced mRNA increase is engendered by transcription of previously quiescent genes. The kinetics and magnitude of changes in mRNA prevalence parallel changes in transcriptional activity; therefore, the ethylene effect is primarily at the level of the transcription. In vivomore » pulse labelling with (/sup 35/S)-methionine showed that between 18 and 27 hours of ethylene treatment a 2.5 fold increase in translational efficiency occurred for one message studied. The resulting protein is the predominant protein synthesized in carrots treated with ethylene for 27 hours. Thus, ethylene exerts multiple regulatory controls on the expression of genetic information.« less

Graphene oxide selectively targets cancer stem cells, across multiple tumor types: Implications for non-toxic cancer treatment, via “differentiation-based nano-therapy”

PubMed Central

Fiorillo, Marco; Verre, Andrea F.; Iliut, Maria; Peiris-Pagés, Maria; Ozsvari, Bela; Gandara, Ricardo; Cappello, Anna Rita; Sotgia, Federica; Vijayaraghavan, Aravind; Lisanti, Michael P.

2015-01-01

Tumor-initiating cells (TICs), a.k.a. cancer stem cells (CSCs), are difficult to eradicate with conventional approaches to cancer treatment, such as chemo-therapy and radiation. As a consequence, the survival of residual CSCs is thought to drive the onset of tumor recurrence, distant metastasis, and drug-resistance, which is a significant clinical problem for the effective treatment of cancer. Thus, novel approaches to cancer therapy are needed urgently, to address this clinical need. Towards this end, here we have investigated the therapeutic potential of graphene oxide to target cancer stem cells. Graphene and its derivatives are well-known, relatively inert and potentially non-toxic nano-materials that form stable dispersions in a variety of solvents. Here, we show that graphene oxide (of both big and small flake sizes) can be used to selectively inhibit the proliferative expansion of cancer stem cells, across multiple tumor types. For this purpose, we employed the tumor-sphere assay, which functionally measures the clonal expansion of single cancer stem cells under anchorage-independent conditions. More specifically, we show that graphene oxide effectively inhibits tumor-sphere formation in multiple cell lines, across 6 different cancer types, including breast, ovarian, prostate, lung and pancreatic cancers, as well as glioblastoma (brain). In striking contrast, graphene oxide is non-toxic for “bulk” cancer cells (non-stem) and normal fibroblasts. Mechanistically, we present evidence that GO exerts its striking effects on CSCs by inhibiting several key signal transduction pathways (WNT, Notch and STAT-signaling) and thereby inducing CSC differentiation. Thus, graphene oxide may be an effective non-toxic therapeutic strategy for the eradication of cancer stem cells, via differentiation-based nano-therapy. PMID:25708684

Protective effect of astaxanthin against multiple organ injury in a rat model of sepsis.

PubMed

Zhou, Liping; Gao, Min; Xiao, Zhiming; Zhang, Juan; Li, Xiangmin; Wang, Aimin

2015-05-15

Astaxanthin, a xanthophyll carotenoid, holds exceptional promise as an antioxidant, anti-inflammatory, and anticancer agent. No evidence has been published whether it has protective effects on sepsis. The study aimed to investigate the potential effects of astaxanthin on sepsis and multiple organ dysfunctions. Sepsis was induced by cecal ligation and puncture (CLP) in Sprague-Dawley rats. Animals subjected to CLP and sham-operated control rats were given vehicle or astaxanthin 100 mg/kg/d by oral gavage for 7 d before the operation. The rats were killed at the indicated time points, and the specimen was collected. Cytokines and multiorgan injury-associated enzymatic and oxidative stress indicators were investigated. Multiorgan tissues were assessed histologically, the peritoneal bacterial load and the 72-h survival was observed too. Sepsis resulted in a significant increase in serum tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels showing systemic inflammatory response; it also caused a remarkable decrease in the superoxide dismutase activity and a significant increase in the malondialdehyde content showing oxidative damage; sepsis caused a great increase in organ injury-associated indicators, including blood urea nitrogen, creatinine, lactate dehydrogenase, creatine kinase isoenzyme-MB isotype, alanine aminotransferase, and aspartate aminotransferase, which was confirmed by histologic examination. And there was a dramatical increase of colony-forming units in the peritoneal cavity in septic rats. Astaxanthin reversed these inflammatory and oxidant response, alleviated the organ injury, reduced the peritoneal bacterial load, and improved the survival of septic rats induced by CLP. Astaxanthin exerts impressively protective effects on CLP-induced multiple organ injury. It might be used as a potential treatment for clinical sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study.

PubMed

Miller, David H; Fox, Robert J; Phillips, J Theodore; Hutchinson, Michael; Havrdova, Eva; Kita, Mariko; Wheeler-Kingshott, Claudia A M; Tozer, Daniel J; MacManus, David G; Yousry, Tarek A; Goodsell, Mary; Yang, Minhua; Zhang, Ray; Viglietta, Vissia; Dawson, Katherine T

2015-03-17

To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment. © 2015 American Academy of Neurology.

MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis

PubMed Central

Mao, Peizhong; Manczak, Maria; Shirendeb, Ulziibat P.; Reddy, P. Hemachandra

2013-01-01

Oxidative stress and mitochondrial dysfunction are involved in the progression and pathogenesis of multiple sclerosis (MS). MitoQ is a mitochondria-targeted antioxidant that has a neuroprotective role in several mitochondrial and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Here we sought to determine the possible effects of a systematic administration of MitoQ as a therapy, using an experimental autoimmune encephalomyelitis (EAE) mouse model. We studied the beneficial effects of MitoQ in EAE mice that mimic MS like symptoms by treating EAE mice with MitoQ and pretreated C57BL6 mice MitoQ plus EAE induction. We found that pretreatment and treatment of EAE mice with MitoQ reduced neurological disabilities associated with EAE. We also found that both pretreatment and treatment of the EAE mice with MitoQ significantly suppressed inflammatory markers of EAE, including the inhibition of inflammatory cytokines and chemokines. MitoQ treatments reduced neuronal cell loss in the spinal cord, a factor underlying motor disability in EAE mice. The neuroprotective role of MitoQ was confirmed by a neuron-glia co-culture system designed to mimic the mechanism of MS and EAE in vitro. We found that axonal inflammation and oxidative stress are associated with impaired behavioral functions in the EAE mouse model and that treatment with MitoQ can exert protective effects on neurons and reduce axonal inflammation and oxidative stress. These protective effects are likely via multiple mechanisms, including the attenuation of the robust immune response. These results suggest that MitoQ may be a new candidate for the treatment of MS. PMID:24055980

MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

PubMed

Mao, Peizhong; Manczak, Maria; Shirendeb, Ulziibat P; Reddy, P Hemachandra

2013-12-01

Oxidative stress and mitochondrial dysfunction are involved in the progression and pathogenesis of multiple sclerosis (MS). MitoQ is a mitochondria-targeted antioxidant that has a neuroprotective role in several mitochondrial and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Here we sought to determine the possible effects of a systematic administration of MitoQ as a therapy, using an experimental autoimmune encephalomyelitis (EAE) mouse model. We studied the beneficial effects of MitoQ in EAE mice that mimic MS like symptoms by treating EAE mice with MitoQ and pretreated C57BL6 mice with MitoQ plus EAE induction. We found that pretreatment and treatment of EAE mice with MitoQ reduced neurological disabilities associated with EAE. We also found that both pretreatment and treatment of the EAE mice with MitoQ significantly suppressed inflammatory markers of EAE, including the inhibition of inflammatory cytokines and chemokines. MitoQ treatments reduced neuronal cell loss in the spinal cord, a factor underlying motor disability in EAE mice. The neuroprotective role of MitoQ was confirmed by a neuron-glia co-culture system designed to mimic the mechanism of MS and EAE in vitro. We found that axonal inflammation and oxidative stress are associated with impaired behavioral functions in the EAE mouse model and that treatment with MitoQ can exert protective effects on neurons and reduce axonal inflammation and oxidative stress. These protective effects are likely via multiple mechanisms, including the attenuation of the robust immune response. These results suggest that MitoQ may be a new candidate for the treatment of MS. © 2013.

Lysophosphatidic Acid (LPA) Signaling in Human and Ruminant Reproductive Tract

PubMed Central

Wocławek-Potocka, Izabela; Rawińska, Paulina; Kowalczyk-Zieba, Ilona; Boruszewska, Dorota; Sinderewicz, Emilia; Waśniewski, Tomasz; Skarzynski, Dariusz Jan

2014-01-01

Lysophosphatidic acid (LPA) through activating its G protein-coupled receptors (LPAR 1–6) exerts diverse cellular effects that in turn influence several physiological processes including reproductive function of the female. Studies in various species of animals and also in humans have identified important roles for the receptor-mediated LPA signaling in multiple aspects of human and animal reproductive tract function. These aspects range from ovarian and uterine function, estrous cycle regulation, early embryo development, embryo implantation, decidualization to pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and reproductive tissue associated tumors. The review describes recent progress in LPA signaling research relevant to human and ruminant reproduction, pointing at the cow as a relevant model to study LPA influence on the human reproductive performance. PMID:24744506

The response of the host microcirculation to bacterial sepsis: does the pathogen matter?

PubMed

Legrand, Matthieu; Klijn, Eva; Payen, Didier; Ince, Can

2010-02-01

Sepsis results from the interaction between a host and an invading pathogen. The microcirculatory dysfunction is now considered central in the development of the often deadly multiple organ dysfunction syndrome in septic shock patients. The microcirculatory flow shutdown and flow shunting leading to oxygen demand and supply mismatch at the cellular level and the local activation of inflammatory pathways resulting from the leukocyte-endothelium interactions are both features of the sepsis-induced microcirculatory dysfunction. Although the host response through the inflammatory and immunologic response appears to be critical, there are also evidences that Gram-positive and Gram-negative bacteria can exert different effects at the microcirculatory level. In this review we discuss available data on the potential bacterial-specific microcirculatory alterations observed during sepsis.

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

Dynamic interactions between cells and their extracellular matrix mediate embryonic development.

PubMed

Goody, Michelle F; Henry, Clarissa A

2010-06-01

Cells and their surrounding extracellular matrix microenvironment interact throughout all stages of life. Understanding the continuously changing scope of cell-matrix interactions in vivo is crucial to garner insights into both congenital birth defects and disease progression. A current challenge in the field of developmental biology is to adapt in vitro tools and rapidly evolving imaging technology to study cell-matrix interactions in a complex 4-D environment. In this review, we highlight the dynamic modulation of cell-matrix interactions during development. We propose that individual cell-matrix adhesion proteins are best considered as complex proteins that can play multiple, often seemingly contradictory roles, depending upon the context of the microenvironment. In addition, cell-matrix proteins can also exert different short versus long term effects. It is thus important to consider cell behavior in light of the microenvironment because of the constant and dynamic reciprocal interactions occurring between them. Finally, we suggest that analysis of cell-matrix interactions at multiple levels (molecules, cells, tissues) in vivo is critical for an integrated understanding because different information can be acquired from all size scales. Copyright 2010 Wiley-Liss, Inc.

Conflicting Demands of Abstract and Specific Visual Object Processing Resolved by Fronto-Parietal Networks

PubMed Central

McMenamin, Brenton W.; Marsolek, Chad J.; Morseth, Brianna K.; Speer, MacKenzie F.; Burton, Philip C.; Burgund, E. Darcy

2016-01-01

Object categorization and exemplar identification place conflicting demands on the visual system, yet humans easily perform these fundamentally contradictory tasks. Previous studies suggest the existence of dissociable visual processing subsystems to accomplish the two abilities – an abstract category (AC) subsystem that operates effectively in the left hemisphere, and a specific exemplar (SE) subsystem that operates effectively in the right hemisphere. This multiple subsystems theory explains a range of visual abilities, but previous studies have not explored what mechanisms exist for coordinating the function of multiple subsystems and/or resolving the conflicts that would arise between them. We collected functional MRI data while participants performed two variants of a cue-probe working memory task that required AC or SE processing. During the maintenance phase of the task, the bilateral intraparietal sulcus (IPS) exhibited hemispheric asymmetries in functional connectivity consistent with exerting proactive control over the two visual subsystems: greater connectivity to the left hemisphere during the AC task, and greater connectivity to the right hemisphere during the SE task. Moreover, probe-evoked activation revealed activity in a broad fronto-parietal network (containing IPS) associated with reactive control when the two visual subsystems were in conflict, and variations in this conflict signal across trials was related to the visual similarity of the cue/probe stimulus pairs. Although many studies have confirmed the existence of multiple visual processing subsystems, this study is the first to identify the mechanisms responsible for coordinating their operations. PMID:26883940

Conflicting demands of abstract and specific visual object processing resolved by frontoparietal networks.

PubMed

McMenamin, Brenton W; Marsolek, Chad J; Morseth, Brianna K; Speer, MacKenzie F; Burton, Philip C; Burgund, E Darcy

2016-06-01

Object categorization and exemplar identification place conflicting demands on the visual system, yet humans easily perform these fundamentally contradictory tasks. Previous studies suggest the existence of dissociable visual processing subsystems to accomplish the two abilities-an abstract category (AC) subsystem that operates effectively in the left hemisphere and a specific exemplar (SE) subsystem that operates effectively in the right hemisphere. This multiple subsystems theory explains a range of visual abilities, but previous studies have not explored what mechanisms exist for coordinating the function of multiple subsystems and/or resolving the conflicts that would arise between them. We collected functional MRI data while participants performed two variants of a cue-probe working memory task that required AC or SE processing. During the maintenance phase of the task, the bilateral intraparietal sulcus (IPS) exhibited hemispheric asymmetries in functional connectivity consistent with exerting proactive control over the two visual subsystems: greater connectivity to the left hemisphere during the AC task, and greater connectivity to the right hemisphere during the SE task. Moreover, probe-evoked activation revealed activity in a broad frontoparietal network (containing IPS) associated with reactive control when the two visual subsystems were in conflict, and variations in this conflict signal across trials was related to the visual similarity of the cue-probe stimulus pairs. Although many studies have confirmed the existence of multiple visual processing subsystems, this study is the first to identify the mechanisms responsible for coordinating their operations.

Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands.

PubMed

Sancineto, Luca; Iraci, Nunzio; Barreca, Maria Letizia; Massari, Serena; Manfroni, Giuseppe; Corazza, Gianmarco; Cecchetti, Violetta; Marcello, Alessandro; Daelemans, Dirk; Pannecouque, Christophe; Tabarrini, Oriana

2014-09-01

It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of Layer Thickness, Raster Angle, Deformation Temperature and Recovery Temperature on the Shape-Memory Effect of 3D-Printed Polylactic Acid Samples

PubMed Central

Wu, Wenzheng; Ye, Wenli; Wu, Zichao; Geng, Peng; Wang, Yulei; Zhao, Ji

2017-01-01

The success of the 3D-printing process depends upon the proper selection of process parameters. However, the majority of current related studies focus on the influence of process parameters on the mechanical properties of the parts. The influence of process parameters on the shape-memory effect has been little studied. This study used the orthogonal experimental design method to evaluate the influence of the layer thickness H, raster angle θ, deformation temperature Td and recovery temperature Tr on the shape-recovery ratio Rr and maximum shape-recovery rate Vm of 3D-printed polylactic acid (PLA). The order and contribution of every experimental factor on the target index were determined by range analysis and ANOVA, respectively. The experimental results indicated that the recovery temperature exerted the greatest effect with a variance ratio of 416.10, whereas the layer thickness exerted the smallest effect on the shape-recovery ratio with a variance ratio of 4.902. The recovery temperature exerted the most significant effect on the maximum shape-recovery rate with the highest variance ratio of 1049.50, whereas the raster angle exerted the minimum effect with a variance ratio of 27.163. The results showed that the shape-memory effect of 3D-printed PLA parts depended strongly on recovery temperature, and depended more weakly on the deformation temperature and 3D-printing parameters. PMID:28825617

Pharmacodynamic studies of vancomycin, metronidazole and fusidic acid against Clostridium difficile.

PubMed

Odenholt, Inga; Walder, Mats; Wullt, Marlene

2007-01-01

Pharmacodynamic studies of antibiotics have attracted great interest in recent years. However, studies on the pharmacodynamics of different antibiotics against Clostridium difficile are scarce. The postantibiotic effects (PAE) and the postantibiotic sub-minimum inhibitory concentration (MIC) effects (PA SME) of vancomycin, metronidazole and fusidic acid were investigated by viable counts against three different strains of C. difficile. The killing rate and extent of the three antibiotics against the same strains were also studied by adding 2, 4, 8, 16 and 32x MIC of the three antibiotics, respectively. Metronidazole exerted a very rapid bactericidal effect at concentrations of 8x MIC and above against all three strains investigated. Vancomycin gave overall less kill in comparison to metronidazole and was bacteriostatic against two of the three strains. Fusidic acid exerted a concentration-dependent killing against two of the strains. Vancomycin exerted short PAEs and PA SMEs against all three strains. Significantly longer PAEs and PA SMEs were noted for fusidic acid. Metronidazole gave similar short PAEs like vancomycin but longer PA SMEs were noted against two of the investigated strains. Metronidazole exerted the most prominent bactericidal effect greater than fusidic acid and greater than vancomycin. Fusidic acid gave overall the longest PAEs and PA SMEs greater than metronidazole and greater than vancomycin. Copyright 2007 S. Karger AG, Basel.

Metabolic changes of cultured DRG neurons induced by adenosine using confocal microscopy imaging

NASA Astrophysics Data System (ADS)

Zheng, Liqin; Huang, Yimei; Chen, Jiangxu; Wang, Yuhua; Yang, Hongqin; Zhang, Yanding; Xie, Shusen

2012-12-01

Adenosine exerts multiple effects on pain transmission in the peripheral nervous system. This study was performed to use confocal microscopy to evaluate whether adenosine could affect dorsal root ganglia (DRG) neurons in vitro and test which adenosine receptor mediates the effect of adenosine on DRG neurons. After adding adenosine with different concentration, we compared the metabolic changes by the real time imaging of calcium and mitochondria membrane potential using confocal microscopy. The results showed that the effect of 500 μM adenosine on the metabolic changes of DRG neurons was more significant than others. Furthermore, four different adenosine receptor antagonists were used to study which receptor mediated the influences of adenosine on the cultured DRG neurons. All adenosine receptor antagonists especially A1 receptor antagonist (DPCPX) had effect on the Ca2+ and mitochondria membrane potential dynamics of DRG neurons. The above studies demonstrated that the effect of adenosine which may be involved in the signal transmission on the sensory neurons was dose-dependent, and all the four adenosine receptors especially the A1R may mediate the transmission.

Anthropogenic pollutants: a threat to ecosystem sustainability?

PubMed

Rhind, S M

2009-11-27

Pollutants, including synthetic organic materials and heavy metals, are known to adversely affect physiological systems in all animal species studied to date. While many individual chemicals can perturb normal functions, the combined actions of multiple pollutants are of particular concern because they can exert effects even when each individual chemical is present at concentrations too low to be individually effective. The biological effects of pollutants differ greatly between species reflecting differences in the pattern of exposure, routes of uptake, metabolism following uptake, rates of accumulation and sensitivity of the target organs. Thus, understanding of the effects of pollutants on wildlife and ecosystems will require detailed study of many different species, representing a wide range of taxa. However, such studies can be informed by knowledge obtained in more controlled conditions which may indicate likely mechanisms of action and suitable endpoint measurements. Responses may be exacerbated by interactions between the effects of pollutants and environmental stressors, such as under-nutrition or osmotic stresses and so changes in such variables associated with climatic changes may exacerbate physiological responses to pollutant burdens.

Defining the Focus of Attention: Effects of Attention on Perceived Exertion and Fatigue

PubMed Central

Lohse, Keith R.; Sherwood, David E.

2011-01-01

This manuscript presents two experiments designed to explore the effects of attention on perceived exertion and time to failure in a fatiguing athletic task. There were two major motivating factors for these experiments. First, there are few studies evaluating attentional focus effects in endurance tasks and, second, there is a lack of integration between studies of attentional focus as external/internal (e.g., Wulf, 2007a) compared to associative/dissociative (e.g., Stevinson and Biddle, 1998). In Experiment 1, we used a fatiguing wall-sit posture (essentially a complex, isometric task) to compare two different types of external attention with an internal focus on the position of the legs. An external focus (regardless of type) increased the time taken to failure and reduced perceived exertion. In Experiment 2, we manipulated subjects’ expectancy of fatigue to test the interaction of attention and expectancy (both top-down factors) in this highly fatiguing task. Previous theories of attention during endurance tasks have suggested that as fatigue/pain increase, bottom-up factors begin to dominate subjects’ attention. While this may be true, Experiment 2 showed that even in a highly fatiguing task, attentional strategies, and expectancies affected the time to failure and perceived exertion. PMID:22102843

Reverse ego-depletion: Acts of self-control can improve subsequent performance in Indian cultural contexts.

PubMed

Savani, Krishna; Job, Veronika

2017-10-01

The strength model of self-control has been predominantly tested with people from Western cultures. The present research asks whether the phenomenon of ego-depletion generalizes to a culture emphasizing the virtues of exerting mental self-control in everyday life. A pilot study found that whereas Americans tended to believe that exerting willpower on mental tasks is depleting, Indians tended to believe that exerting willpower is energizing. Using dual task ego-depletion paradigms, Studies 1a, 1b, and 1c found reverse ego-depletion among Indian participants, such that participants exhibited better mental self-control on a subsequent task after initially working on strenuous rather than nonstrenuous cognitive tasks. Studies 2 and 3 found that Westerners exhibited the ego-depletion effect whereas Indians exhibited the reverse ego-depletion effect on the same set of tasks. Study 4 documented the causal effect of lay beliefs about whether exerting willpower is depleting versus energizing on reverse ego-depletion with both Indian and Western participants. Together, these studies reveal the underlying basis of the ego-depletion phenomenon in culturally shaped lay theories about willpower. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Comparison between tocotrienol and omeprazole on gastric growth factors in stress-exposed rats.

PubMed

Nur Azlina, Mohd Fahami; Qodriyah, Hj Mohd Saad; Chua, Kien Hui; Kamisah, Yusof

2017-08-28

To investigate and compare the effects of tocotrienol and omeprazole on gastric growth factors in rats exposed to water-immersion restraint stress (WIRS). Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) by oral gavage. After 28 d of treatment, rats from one control group and both treated groups were subjected to WIRS one time for 3.5 h. Gastric lesions were measured and gastric tissues were obtained to measure vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-alpha (TGF-α) mRNA expression. Rats exposed to WIRS for 3.5 h demonstrated the presence of considerable ulcers in the form of gastric erosion. The lesion index in the stressed control (S) group was increased ( P < 0.001) compared to the tocotrienol treated and omeprazole treated groups. Stress led to a decrease in gastric VEGF ( P < 0.001), bFGF ( P < 0.001) and TGF-α ( P < 0.001) mRNA levels and caused an increase in EGF mRNA ( P < 0.001) that was statistically significant compared to the non-stressed control group. Although both treatment agents exerted similar ulcer reducing ability, only treatment with tocotrienol led to increased expression of VEGF ( P = 0.008), bFGF ( P = 0.001) and TGF-α ( P = 0.002) mRNA. Tocotrienol provides gastroprotective effects in WIRS-induced ulcers. Compared to omeprazole, tocotrienol exerts a similar protective effect, albeit through multiple mechanisms of protection, particularly through up-regulation of growth factors that assist in repair of gastric tissue injuries.

Upper Extremity Compartment Syndrome in a Patient with Acute Gout Attack but without Trauma or Other Typical Causes.

PubMed

Skedros, John G; Smith, James S; Henrie, Marshall K; Finlinson, Ethan D; Trachtenberg, Joel D

2018-01-01

We report the case of a 30-year-old Polynesian male with a severe gout flare of multiple joints and simultaneous acute compartment syndrome (ACS) of his right forearm and hand without trauma or other typical causes. He had a long history of gout flares, but none were known to be associated with compartment syndrome. He also had concurrent infections in his right elbow joint and olecranon bursa. A few days prior to this episode of ACS, high pain and swelling occurred in his right upper extremity after a minimal workout with light weights. A similar episode occurred seven months prior and was attributed to a gout flare. Unlike past flares that resolved with colchicine and/or anti-inflammatory medications, his current upper extremity pain/swelling worsened and became severe. Hand and forearm fasciotomies were performed. Workup included general medicine, rheumatology and infectious disease consultations, myriad blood tests, and imaging studies including Doppler ultrasound and CT angiography. Additional clinical history suggested that he had previously unrecognized recurrent exertional compartment syndrome that led to the episode of ACS reported here. Chronic exertional compartment syndrome (CECS) presents a difficult diagnosis when presented with multiple symptoms concurrently. This case provides an example of one such diagnosis.

Upper Extremity Compartment Syndrome in a Patient with Acute Gout Attack but without Trauma or Other Typical Causes

PubMed Central

Smith, James S.; Henrie, Marshall K.; Finlinson, Ethan D.; Trachtenberg, Joel D.

2018-01-01

We report the case of a 30-year-old Polynesian male with a severe gout flare of multiple joints and simultaneous acute compartment syndrome (ACS) of his right forearm and hand without trauma or other typical causes. He had a long history of gout flares, but none were known to be associated with compartment syndrome. He also had concurrent infections in his right elbow joint and olecranon bursa. A few days prior to this episode of ACS, high pain and swelling occurred in his right upper extremity after a minimal workout with light weights. A similar episode occurred seven months prior and was attributed to a gout flare. Unlike past flares that resolved with colchicine and/or anti-inflammatory medications, his current upper extremity pain/swelling worsened and became severe. Hand and forearm fasciotomies were performed. Workup included general medicine, rheumatology and infectious disease consultations, myriad blood tests, and imaging studies including Doppler ultrasound and CT angiography. Additional clinical history suggested that he had previously unrecognized recurrent exertional compartment syndrome that led to the episode of ACS reported here. Chronic exertional compartment syndrome (CECS) presents a difficult diagnosis when presented with multiple symptoms concurrently. This case provides an example of one such diagnosis. PMID:29796328

Perceived exertion is as effective as the perceptual strain index in predicting physiological strain when wearing personal protective clothing.

PubMed

Borg, David N; Costello, Joseph T; Bach, Aaron J; Stewart, Ian B

2017-02-01

The perceptual strain index (PeSI) has been shown to overcome the limitations associated with the assessment of the physiological strain index (PSI), primarily the need to obtain a core body temperature measurement. The PeSI uses the subjective scales of thermal sensation and perceived exertion (RPE) to provide surrogate measures of core temperature and heart rate, respectively. Unfortunately, thermal sensation has shown large variability in providing an estimation of core body temperature. Therefore, the primary aim of this study was to determine if thermal comfort improved the ability of the PeSI to predict the PSI during exertional-heat stress. Eighteen healthy males (age: 23.5years; body mass: 79.4kg; maximal aerobic capacity: 57.2ml·kg -1 ·min -1 ) wore four different chemical/biological protective garments while walking on treadmill at a low (<325W) or moderate (326-499W) metabolic workload in environmental conditions equivalent to wet bulb globe temperatures 21, 30 or 37°C. Trials were terminated when heart rate exceeded 90% of maximum, when core body temperature reached 39°C, at 120min or due to volitional fatigue. Core body temperature, heart rate, thermal sensation, thermal comfort and RPE were recorded at 15min intervals and at termination. Multiple statistical methods were used to determine the most accurate perceptual predictor. Significant moderate relationships were observed between the PeSI (r=0.74; p<0.001), the modified PeSI (r=0.73; p<0.001) and unexpectedly RPE (r=0.71; p<0.001) with the PSI, respectively. The PeSI (mean bias: -0.8±1.5 based on a 0-10 scale; area under the curve: 0.887), modified PeSI (mean bias: -0.5±1.4 based on 0-10 scale; area under the curve: 0.886) and RPE (mean bias: -0.7±1.4 based on a 0-10 scale; area under the curve: 0.883) displayed similar predictive performance when participants experienced high-to-very high levels of physiological strain. Modifying the PeSI did not improve the subjective prediction of physiological strain. However, RPE provided an equally accurate prediction of physiological strain, particularly when high-to-very high levels of strain were observed. Therefore, given its predictive performance and user-friendliness, the evidence suggests that RPE in isolation is a practical and cost-effective tool able to estimate physiological strain during exertional-heat stress under these work conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease.

PubMed

Yamamoto, Shinji; Yamashina, Kota; Ishikawa, Masaki; Gotoh, Mari; Yagishita, Sosuke; Iwasa, Kensuke; Maruyama, Kei; Murakami-Murofushi, Kimiko; Yoshikawa, Keisuke

2017-07-21

Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. We reported earlier that cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death. We designed, chemically synthesized, and metabolically stabilized derivatives of cPA: 2-carba-cPA (2ccPA), a synthesized compound in which one of the phosphate oxygen molecules is replaced with a methylene group at the sn-2 position. In the present study, we investigated whether 2ccPA exerts protective effects in oligodendrocytes and suppresses pathology in the two most common mouse models of multiple sclerosis. To evaluate whether 2ccPA has potential beneficial effects on the pathology of multiple sclerosis, we investigated the effects of 2ccPA on oligodendrocyte cell death in vitro and administrated 2ccPA to mouse models of experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination. We demonstrated that 2ccPA suppressed the CoCl 2 -induced increase in the Bax/Bcl-2 protein expression ratio and phosphorylation levels of p38MAPK and JNK protein. 2ccPA treatment reduced cuprizone-induced demyelination, microglial activation, NLRP3 inflammasome, and motor dysfunction. Furthermore, 2ccPA treatment reduced autoreactive T cells and macrophages, spinal cord injury, and pathological scores in EAE, the autoimmune multiple sclerosis mouse model. We demonstrated that 2ccPA protected oligodendrocytes via suppression of the mitochondrial apoptosis pathway. Also, we found beneficial effects of 2ccPA in the multiperiod of cuprizone-induced demyelination and the pathology of EAE. These data indicate that 2ccPA may be a promising compound for the development of new drugs to treat demyelinating disease and ameliorate the symptoms of multiple sclerosis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, E.; Suzuki, S.; Tsuzuki, H.

Mice were subcutaneoulsy injected with Sr/sup 90/ or Sr/sup 85/, and effects of various drugs on their 3-day excretion and retention on the 4th day were investigated. Among chelating agents, NaCa citrate, NaMg citrate, NaSr citrate, Achromycin (or tetracycline), and aspartic MgK (alone or in combination with NH/sub 4/Cl) displayed Sr-eliminating effects. ATP increased only the excretion without diminishing the retention in bone. EDTA, DTPA, BADE, tricarballylate, Na citrate and NaPb citrate were not effective. Among salts, Mg salt, sulfite, and thiosulfate were effective in eliminating Sr. The last exerted a greater effect when given concurrently with Mg, Ca, ormore » Sr salt. Ca and Sr salt exerted no effect, and ammonium chloride promoted only urinary secretion, not extending to local or total excretion. Such salts as induce alkalosis conversely exerted inhibitory effects. Among hormones, glucocorticoids had Sreliminating effects. TSH was effective, and antithyroidal drugs conversely seemed to have excretion-diminishing effects. Among vitamins, cocarboxylase increased Sr excretion, but did not decrease the retention in bone. Also metabolic inhibitors were ineffective, and NaF conversely increased bone deposition of Sr. Among diuretics, SHdrugs, and weak chelating agents, there were no effective drugs. (JAIF)« less

Independent effects of relevance and arousal on deductive reasoning.

PubMed

Caparos, Serge; Blanchette, Isabelle

2017-08-01

Emotional content can have either a deleterious or a beneficial impact on logicality. Using standard deductive-reasoning tasks, we tested the hypothesis that the interplay of two factors - personal relevance and arousal - determines the nature of the effect of emotional content on logicality. Arousal was assessed using measures of skin conductance. Personal relevance was manipulated by asking participants to reason about semantic contents linked to an emotional event that they had experienced or not. Findings showed that (1) personal relevance exerts a positive effect on logicality while arousal exerts a negative effect, and that (2) these effects are independent of each other.

Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

PubMed

Sedel, Frédéric; Bernard, Delphine; Mock, Donald M; Tourbah, Ayman

2016-11-01

Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Seasonal variation in assisted conception cycles and the influence of photoperiodism on outcome in in vitro fertilization cycles.

PubMed

Wood, Simon; Quinn, Alison; Troupe, Stephen; Kingsland, Charles; Lewis-Jones, Iwan

2006-12-01

The effect of seasonality and daylight length on mammalian reproduction leading to spring births has been well established, and is known as photoperiodism. In assisted reproduction there is much greater uncertainty as to the effect of seasonality. This was a 4-year retrospective analysis of 2709 standardised cycles of IVF/ICSI. Data was analysed with regard to the 1642 cycles occurring during the months of extended daylight (Apr-Sept) and those 1067 cycles during winter months of restricted light length (Oct-Mar). The results showed that there was significant improvement in assisted conception outcomes in cycles performed in summer (lighter) months with more efficient ovarian stimulation 766iu v880iu/per oocyte retrieved (p=0.006). There was similarly a significantly improved implantation rate per embryo transferred 11.42% vs 9.35% (p=0.011) and greater clinical pregnancy rate 20% vs 15% (p=0.0033) during summer cycles. This study appears to demonstrate a significant benefit of increased daylight length on outcomes of IVF/ICSI cycles. Whilst the exact mechanism of this is unclear, it would seem probable that melatonin may have actions at multiple sites and on multiple levels of the reproductive tract, and may exert a more profound effect on outcomes of assisted conception cycles than has been previously considered.

Interferon-β1a reduces plasma CD31+ endothelial microparticles (CD31+EMP) in multiple sclerosis

PubMed Central

Sheremata, William A; Jy, Wenche; Delgado, Sylvia; Minagar, Alireza; McLarty, Jerry; Ahn, Yeon

2006-01-01

Background A correlation between plasma CD31+ endothelial microparticles (CD31+EMP) levels and clinical, as well as brain MRI activity, in multiple sclerosis (MS) patients has been previously reported. However, the effect(s) of treatment with interferon-β1a (IFN-β1a) on plasma levels of CD31+EMP has not been assessed. In a prospective study, we measured plasma CD31+EMP levels in 30 patients with relapsing-remitting MS. Methods Using flow cytometry, in a blinded study, we measured plasma CD31+EMP in 30 consecutive patients with relapsing-remitting MS (RRMS) prior to and 4, 12, 24 and 52 weeks after initiation of intramuscular therapy with interferon-β1a (IFN-β1a), 30 micrograms weekly. At each visit, clinical examination was performed and expanded disability status scale (EDSS) scores were assessed. Results Plasma levels of CD31+EMP were significantly reduced from 24 through 52 weeks following initiation of treatment with IFN-β1a. Conclusion Our data suggest that serial measurement of plasma CD31+EMP levels may be used as a surrogate marker of response to therapy with INF-β1a. In addition, the decline in plasma levels of CD31+EMP further supports the concept that IFN-β1a exerts stabilizing effect on the cerebral endothelial cells in pathogenesis of MS. PMID:16952316

Interferon-beta1a reduces plasma CD31+ endothelial microparticles (CD31+EMP) in multiple sclerosis.

PubMed

Sheremata, William A; Jy, Wenche; Delgado, Sylvia; Minagar, Alireza; McLarty, Jerry; Ahn, Yeon

2006-09-04

A correlation between plasma CD31+ endothelial microparticles (CD31+EMP) levels and clinical, as well as brain MRI activity, in multiple sclerosis (MS) patients has been previously reported. However, the effect(s) of treatment with interferon-beta1a (IFN-beta1a) on plasma levels of CD31+EMP has not been assessed. In a prospective study, we measured plasma CD31+EMP levels in 30 patients with relapsing-remitting MS. Using flow cytometry, in a blinded study, we measured plasma CD31+EMP in 30 consecutive patients with relapsing-remitting MS (RRMS) prior to and 4, 12, 24 and 52 weeks after initiation of intramuscular therapy with interferon-beta1a (IFN-beta1a), 30 micrograms weekly. At each visit, clinical examination was performed and expanded disability status scale (EDSS) scores were assessed. Plasma levels of CD31+EMP were significantly reduced from 24 through 52 weeks following initiation of treatment with IFN-beta1a. Our data suggest that serial measurement of plasma CD31+EMP levels may be used as a surrogate marker of response to therapy with INF-beta1a. In addition, the decline in plasma levels of CD31+EMP further supports the concept that IFN-beta1a exerts stabilizing effect on the cerebral endothelial cells in pathogenesis of MS.

Autophagy regulates the therapeutic potential of mesenchymal stem cells in experimental autoimmune encephalomyelitis

PubMed Central

Dang, Shipeng; Xu, Huanbai; Xu, Congfeng; Cai, Wei; Li, Qian; Cheng, Yiji; Jin, Min; Wang, Ru-Xing; Peng, Yongde; Zhang, Yi; Wu, Changping; He, Xiaozhou; Wan, Bing; Zhang, Yanyun

2014-01-01

Mesenchymal stem cell (MSC)-based therapy is a promising approach to treat various inflammatory disorders including multiple sclerosis. However, the fate of MSCs in the inflammatory microenvironment is largely unknown. Experimental autoimmune encephalomyelitis (EAE) is a well-studied animal model of multiple sclerosis. We demonstrated that autophagy occurred in MSCs during their application for EAE treatment. Inflammatory cytokines, e.g., interferon gamma and tumor necrosis factor, induced autophagy in MSCs synergistically by inducing expression of BECN1/Beclin 1. Inhibition of autophagy by knockdown of Becn1 significantly improved the therapeutic effects of MSCs on EAE, which was mainly attributable to enhanced suppression upon activation and expansion of CD4+ T cells. Mechanistically, inhibition of autophagy increased reactive oxygen species generation and mitogen-activated protein kinase 1/3 activation in MSCs, which were essential for PTGS2 (prostaglandin-endoperoxide synthase 2 [prostaglandin G/H synthase and cyclooxygenase]) and downstream prostaglandin E2 expression to exert immunoregulatory function. Furthermore, pharmacological treatment of MSCs to inhibit autophagy increased their immunosuppressive effects on T cell-mediated EAE. Our findings indicate that inflammatory microenvironment-induced autophagy downregulates the immunosuppressive function of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel strategy to improve MSC-based immunotherapy. PMID:24905997

Autophagy regulates the therapeutic potential of mesenchymal stem cells in experimental autoimmune encephalomyelitis.

PubMed

Dang, Shipeng; Xu, Huanbai; Xu, Congfeng; Cai, Wei; Li, Qian; Cheng, Yiji; Jin, Min; Wang, Ru-Xing; Peng, Yongde; Zhang, Yi; Wu, Changping; He, Xiaozhou; Wan, Bing; Zhang, Yanyun

2014-07-01

Mesenchymal stem cell (MSC)-based therapy is a promising approach to treat various inflammatory disorders including multiple sclerosis. However, the fate of MSCs in the inflammatory microenvironment is largely unknown. Experimental autoimmune encephalomyelitis (EAE) is a well-studied animal model of multiple sclerosis. We demonstrated that autophagy occurred in MSCs during their application for EAE treatment. Inflammatory cytokines, e.g., interferon gamma and tumor necrosis factor, induced autophagy in MSCs synergistically by inducing expression of BECN1/Beclin 1. Inhibition of autophagy by knockdown of Becn1 significantly improved the therapeutic effects of MSCs on EAE, which was mainly attributable to enhanced suppression upon activation and expansion of CD4(+) T cells. Mechanistically, inhibition of autophagy increased reactive oxygen species generation and mitogen-activated protein kinase 1/3 activation in MSCs, which were essential for PTGS2 (prostaglandin-endoperoxide synthase 2 [prostaglandin G/H synthase and cyclooxygenase]) and downstream prostaglandin E2 expression to exert immunoregulatory function. Furthermore, pharmacological treatment of MSCs to inhibit autophagy increased their immunosuppressive effects on T cell-mediated EAE. Our findings indicate that inflammatory microenvironment-induced autophagy downregulates the immunosuppressive function of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel strategy to improve MSC-based immunotherapy.

Minocycline affects human neutrophil respiratory burst and transendothelial migration.

PubMed

Parenti, Astrid; Indorato, Boris; Paccosi, Sara

2017-02-01

This study aimed at investigating the in vitro activity of minocycline and doxycycline on human polymorphonuclear (h-PMN) cell function. h-PMNs were isolated from whole venous blood of healthy subjects; PMN oxidative burst was measured by monitoring ROS-induced oxidation of luminol and transendothelial migration was studied by measuring PMN migration through a monolayer of human umbilical vein endothelial cells. Differences between multiple groups were determined by ANOVA followed by Tukey's multiple comparison test; Student's t test for unpaired data for two groups. Minocycline (1-300 µM) concentration dependently and significantly inhibited oxidative burst of h-PMNs stimulated with 100 nM fMLP. Ten micromolar concentrations, which are superimposable to C max following a standard oral dose of minocycline, promoted a 29.8 ± 4 % inhibition of respiratory burst (P < 0.001; n = 6). Doxycycline inhibited ROS production with a lesser extent and at higher concentrations. 10-100 µM minocycline impaired PMN transendothelial migration, with maximal effect at 100 µM (42.5 ± 7 %, inhibition, n = 5, P < 0.001). These results added new insight into anti-inflammatory effects of minocycline exerted on innate immune h-PMN cell function.

Sex-biased chromatin and regulatory cross-talk between sex chromosomes, autosomes, and mitochondria

PubMed Central

2014-01-01

Several autoimmune and neurological diseases exhibit a sex bias, but discerning the causes and mechanisms of these biases has been challenging. Sex differences begin to manifest themselves in early embryonic development, and gonadal differentiation further bifurcates the male and female phenotypes. Even at this early stage, however, there is evidence that males and females respond to environmental stimuli differently, and the divergent phenotypic responses may have consequences later in life. The effect of prenatal nutrient restriction illustrates this point, as adult women exposed to prenatal restrictions exhibited increased risk factors of cardiovascular disease, while men exposed to the same condition did not. Recent research has examined the roles of sex-specific genes, hormones, chromosomes, and the interactions among them in mediating sex-biased phenotypes. Such research has identified testosterone, for example, as a possible protective agent against autoimmune disorders and an XX chromosome complement as a susceptibility factor in murine models of lupus and multiple sclerosis. Sex-biased chromatin is an additional and likely important component. Research suggesting a role for X and Y chromosome heterochromatin in regulating epigenetic states of autosomes has highlighted unorthodox mechanisms of gene regulation. The crosstalk between the Y chromosomes and autosomes may be further mediated by the mitochondria. The organelles have solely maternal transmission and exert differential effects on males and females. Altogether, research supports the notion that the interaction between sex-biased elements might exert novel regulatory functions in the genome and contribute to sex-specific susceptibilities to autoimmune and neurological diseases. PMID:24422881

Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory

PubMed Central

Balaguer-Ballester, Emili; Seamans, Jeremy K.; Phillips, Anthony G.; Durstewitz, Daniel

2015-01-01

Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines. PMID:26180194

Proteomic investigating the cooperative lethal effect of EGFR and MDM2 inhibitors on ovarian carcinoma.

PubMed

Chang, Shing-Jyh; Liao, En-Chi; Yeo, Hsin-Yueh; Kuo, Wen-Hung; Chen, Hsin-Yi; Tsai, Yi-Ting; Wei, Yu-Shan; Chen, Ying-Jen; Wang, Yi-Shiuan; Li, Ji-Min; Shih, Chuan-Chi; Chan, Chia-Hao; Lai, Zih-Yin; Chou, Hsiu-Chuan; Chuang, Yung-Jen; Chan, Hong-Lin

2018-06-01

With the concept of precision medicine, combining multiple molecular-targeting therapies has brought new approaches to current cancer treatments. Malfunction of the tumor suppressor protein, p53 is a universal hallmark in human cancers. Under normal conditions, p53 is degraded through an ubiquitin-proteosome pathway regulated by its negative regulator, MDM2. In contrast, cellular stress such as DNA damage will activate p53 to carry out DNA repair, cell cycle arrest, and apoptosis. In this study, we focused on ovarian carcinoma with high EGFR and MDM2 overexpression rate. We assessed the effects of combined inhibition by MDM2 (JNJ-26854165) and EGFR (gefitinib) inhibitors on various ovarian cell lines to determine the importance of these two molecular targets on cell proliferation. We then used a proteomic strategy to investigate the relationship between MDM2 and EGFR inhibition to explore the underlying mechanisms of how their combined signaling blockades work together to exert cooperative inhibition. Our results demonstrated that all four cell lines were sensitive to both individual and combined, MDM2 and EGFR inhibition. The proteomic analysis also showed that gefitinib/JNJ-treated CAOV3 cells exhibited downregulation of proteins involved in nucleotide biosynthesis such as nucleoside diphosphate kinase B (NME2). In conclusion, our study showed that the combined treatment with JNJ and gefitinib exerted synergistic inhibition on cell proliferation, thereby suggesting the potential application of combining MDM2 inhibitors with EGFR inhibitors for enhancing efficacy in ovarian cancer treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Testing the role of bedforms as controls on the morphodynamics of sandy braided rivers with CFD

NASA Astrophysics Data System (ADS)

Unsworth, C. A.; Nicholas, A. P.; Ashworth, P. J.; Best, J.; Lane, S. N.; Parsons, D. R.; Sambrook Smith, G.; Simpson, C.; Strick, R. J. P.

2017-12-01

Sand-bed rivers are characterised by multiple scales of topography (e.g., channels, bars and bedforms). Small scale topographic features (e.g., dunes) exert a significant influence on coherent flow structures and sediment transport processes, over distances that scale with channel depth. However, the extent to which such dune-scale effects control larger, channel and bar-scale morphology and morphodynamics remains unknown. Moreover, such bedform effects are typically neglected in two-dimensional (depth-averaged) morphodynamic models that are used to simulate river evolution. To evaluate the significance of these issues, we report results from a combined numerical modelling and field monitoring study, undertaken in the South Saskatchewan River, Canada. Numerical simulations were carried out, using the OpenFOAM CFD code, to quantify the mean three-dimensional flow structure within a 90 x 350 m section of channel. To isolate the role of bedforms as a control on flow and sediment transport, two simulations were undertaken. The first used a high-resolution ( 3 cm) bedform-resolving DEM. The second used a filtered DEM in which dunes were removed and only large scale topographic features (e.g., bars, scour pools etc) were resolved. The results of these simulations are compared here, in order to quantify the degree to which topographic steering by bedforms influences flow and sediment transport directions at bar and channel scales. Analysis of the CFD simulation results within a 2D morphodynamic modelling framework demonstrates that dunes exert a significant influence on sediment transport, and hence morphodynamics, and highlights important shortcomings in existing 2D model parameterisations of topographic steering.

Direction of illumination controls gametophyte orientation in seedless plants and related algae

PubMed Central

Cardona-Correa, Christopher; Ecker, Alice; Graham, Linda E

2015-01-01

The environmental influences that determine dorsiventral or axial gametophyte orientation are unknown for most modern seedless plants. To fill this gap, an experimental laboratory system was employed to evaluate the relative effects of light direction and gravity on body orientation of the dorsiventral green alga Coleochaete orbicularis, and gametophytes of liverworts Blasia pusilla and Marchantia polymorpha, early-diverging moss Sphagnum compactum, and fern Ceratopteris richardii, the latter functioning as experimental control. Replicate clonal cultures were experimentally illuminated only from above, only from below, or from multiple directions, with the same near-saturation PAR level for periods brief enough to minimize nutrient limitation effects, and orientation of new growth was evaluated. For all species tested, direction of illumination exerted stronger control over gametophyte body orientation than gravity. When illuminated only from below: 1) axial Sphagnum gametophores that had initially grown into an overlying air space inverted growth by 180°, burrowing into the substrate; 2) new growth of dorsiventral Blasia, Marchantia, and Ceratopteris gametophytes–whose ventral rhizoids initially penetrated agar substrate and dorsal surfaces initially faced overlying airspace–twisted 180° so that ventral surfaces bearing rhizoids faced overlying air space and rhizoids extended into the air; and 3) Coleochaete lost typical dorsiventral organization and diagnostic dorsal hairs. Direction of illumination also exerted stronger control over orientation of liverwort new growth than surface contact did. These results indicate that early land plants likely inherited light-directed gametophyte body orientation from ancestral streptophyte algae and suggest a mechanism for reorientation of gametophyte-dominant land plants after spatial disturbance. PMID:26237278

Direction of illumination controls gametophyte orientation in seedless plants and related algae.

PubMed

Cardona-Correa, Christopher; Ecker, Alice; Graham, Linda E

2015-01-01

The environmental influences that determine dorsiventral or axial gametophyte orientation are unknown for most modern seedless plants. To fill this gap, an experimental laboratory system was employed to evaluate the relative effects of light direction and gravity on body orientation of the dorsiventral green alga Coleochaete orbicularis, and gametophytes of liverworts Blasia pusilla and Marchantia polymorpha, early-diverging moss Sphagnum compactum, and fern Ceratopteris richardii, the latter functioning as experimental control. Replicate clonal cultures were experimentally illuminated only from above, only from below, or from multiple directions, with the same near-saturation PAR level for periods brief enough to minimize nutrient limitation effects, and orientation of new growth was evaluated. For all species tested, direction of illumination exerted stronger control over gametophyte body orientation than gravity. When illuminated only from below: 1) axial Sphagnum gametophores that had initially grown into an overlying air space inverted growth by 180°, burrowing into the substrate; 2) new growth of dorsiventral Blasia, Marchantia, and Ceratopteris gametophytes-whose ventral rhizoids initially penetrated agar substrate and dorsal surfaces initially faced overlying airspace-twisted 180° so that ventral surfaces bearing rhizoids faced overlying air space and rhizoids extended into the air; and 3) Coleochaete lost typical dorsiventral organization and diagnostic dorsal hairs. Direction of illumination also exerted stronger control over orientation of liverwort new growth than surface contact did. These results indicate that early land plants likely inherited light-directed gametophyte body orientation from ancestral streptophyte algae and suggest a mechanism for reorientation of gametophyte-dominant land plants after spatial disturbance.

Muscular force transmission: a unified, dual or multiple system? A review and some explorative experimental results.

PubMed

Huijing, P

1999-10-01

Structures contributing to force transmission in muscle are reviewed combining some historical and relatively recently published experimental data. Also, effects of aponeurotomy and tenotomy are reviewed shortly as well as some new experimental results regarding these interventions that reinforce the concept of myofascial force transmission. The review is also illustrated by some new images of single muscle fibres from Xenopus Laevis indicative of such transmission and some data about locations of insertion of human gluteus maximus muscle. From this review and the new material, emerges a line of thought indicating that mechanical connections between muscle fibres and intramuscular connective tissue play an important role in force transmission. New experimental observations are presented for non-spanning muscle (i.c., rat biceps femoris muscle), regarding the great variety of types of intramuscular connections that exist i n addition to myo-tendinous junctions at the perimuscular ends of muscle fibres. Such connections are classified as (1) tapered end connections, (2) Myo-myonal junctions, (3) myo-epimysial junctions and (3) Myo-endomysial junctions. This line of thought is followed up by consideration of a possible role of connections of intra- and extramuscular connective tissue in force transmission out of the muscle. Experimental results of an explorative nature, regarding the interactions of extensor digitorum longus (EDL), tibialis anterior (TA) and hallucis longus (HAL) muscles within a relatively intact dorsal flexor compartment of the rat hind leg, indicate that: (1) length force properties of EDL are influenced by TA activity in a length dependent fashion. Depending on TA length, force exerted by EDL, kept at constant origin insertion distance, is variable and the effect is influenced by EDL length itself as well; (2) Force is transmitted from muscle to extramuscular connective tissue and vice versa. As a consequence force exerted at proximal and distal tendons of a muscle are not always equal. The difference being transmitted by extramuscular connective tissue and may appear at the tendons of other muscles or may be transmitted via connective tissue directly to bone. It is concluded that the system of force transmission from skeletal muscle should be considered as a multiple system.

Ways of increasing muscular activity by means of isometric muscular exertion

NASA Technical Reports Server (NTRS)

Kovalik, A. V.

1980-01-01

The effect of isometric muscular exertion on the human body was investigated by having subjects perform basic movements in a sitting position in the conventional manner with additional muscle tension at 50% maximum force and at maximum force. The pulse, arterial pressure, skin temperature, respiratory rate, minute respiratory volume and electrical activity of the muscles involved were all measured. Performance of the exercises with maximum muscular exertion for 20 sec and without movement resulted in the greatest shifts in these indices; in the conventional manner substantial changes did not occur; and with isometric muscular exertion with 50% maximum force with and without movement, optimal functional shifts resulted. The latter is recommended for use in industrial exercises for the prevention of hypodynamia. Ten exercises are suggested.

Effects of Physical Activity on Mathematical Computation among Young Children.

ERIC Educational Resources Information Center

Gabbard, Carl; Barton, Joel

1979-01-01

When 106 second-grade children were tested for simple computation ability in various conditions of induced physical exertion (no exertion v 20, 30, 40, or 50 minutes of activity), significantly higher scores were observed after the 50-minute treatment, and no significant differences were noted between male and female scores. (Author/RL)

Professional Preparation regarding the Recognition and Treatment of Exertional Heat Stroke: The Student Perspective

ERIC Educational Resources Information Center

Mazerolle, Stephanie M.; Pagnotta, Kelly D.; Casa, Douglas J.; Armstrong, Lawrence; Maresh, Carl

2011-01-01

Context: Current evidence suggests rectal temperature(T[subscript re] and cold-water immersion (CWI) are the most effective means to diagnose and treat exertional heat stroke (EHS), respectively. Educators, clinicians, and students should be apprised of this evidence to guide their practice. Objective: Investigate what athletic training students…

Physiological Responses of Two Epiphytic Bryophytes to Nitrogen, Phosphorus and Sulfur Addition in a Subtropical Montane Cloud Forest

PubMed Central

Chen, Xi; Liu, Wen-yao; Song, Liang; Li, Su; Wu, Yi; Shi, Xian-meng; Huang, Jun-biao; Wu, Chuan-sheng

2016-01-01

Atmospheric depositions pose significant threats to biodiversity and ecosystem function. However, the underlying physiological mechanisms are not well understood, and few studies have considered the combined effects and interactions of multiple pollutants. This in situ study explored the physiological responses of two epiphytic bryophytes to combined addition of nitrogen, phosphorus and sulfur. We investigated the electrical conductivity (EC), total chlorophyll concentration (Chl), nutrient stoichiometry and chlorophyll fluorescence signals in a subtropical montane cloud forest in south-west China. The results showed that enhanced fertilizer additions imposed detrimental effects on bryophytes, and the combined enrichment of simulated fertilization exerted limited synergistic effects in their natural environments. On the whole, EC, Chl, the effective quantum yield of photosystem II (ΦPSII) and photochemical quenching (qP) were the more reliable indicators of increased artificial fertilization. However, conclusions on nutrient stoichiometry should be drawn cautiously concerning the saturation uptake and nutrient interactions in bryophytes. Finally, we discuss the limitations of prevailing fertilization experiments and emphasize the importance of long-term data available for future investigations. PMID:27560190

The Effect of Intermittent Vest Cooling on Thermoregulation and Cardiovascular Strain in Baseball Catchers.

PubMed

Bishop, Stacy H; Szymanski, David J; Ryan, Greg A; Herron, Robert L; Bishop, Phil A

2017-08-01

Bishop, SH, Szymanski, DJ, Ryan, GA, Herron, RL, and Bishop, PA. The effect of intermittent vest cooling on thermoregulation and cardiovascular strain in baseball catchers. J Strength Cond Res 31(8): 2060-2065, 2017-Baseball catchers are exposed to multiple physiological challenges while playing outside during the spring and summer months, many of which deal with recovery and thermoregulation. The purpose of this study was to investigate the effect of intermittent cooling on core temperature, cardiovascular strain, exertion, and recovery during a simulated catching performance in the heat. Six trained college-aged baseball catchers performed in a controlled, hot (35° C), and humid (25% relative humidity) environment in a counter-balanced, cross-over design. Ice vest cooling (VC) was used as a cooling modality and was compared with a control of no cooling (NC). Rectal temperature (Tre), heart rate (HR), rating of perceived exertion (RPE), and perceived recovery scale (PRS) were recorded before and after each simulated inning. All activities took place in a heat chamber, and each inning consisted of catchers receiving 12 pitches in their position followed by 6 minutes of recovery. Nine total innings were performed, and 27 total innings were performed with each of the 2 treatments. A significantly smaller mean Tre change was seen in VC when compared with NC (0.58 ± 0.2° C, 0.98 ± 0.2° C, p ≤ 0.01, respectively). Rating of perceived exertion was significantly lower and PRS was significantly improved for VC compared with NC (both p ≤ 0.05). Mean recovery HR during VC was significantly lower than NC in the fifth (VC = 84 ± 8 b·min, NC = 90 ± 9 b·min, p = 0.04), seventh (VC = 84 ± 3 b·min, NC = 92 ± 7 b·min, p = 0.02), and ninth (VC = 85 ± 7 b·min, NC = 93 ± 5 b·min, p = 0.01) innings. Heart rate during catching was significantly lower at the end of the VC trials when compared with NC (108 ± 16 b·min vs. 120 ± 19 b·min, p = 0.02, respectively). Vest cooling decreased heat strain, cardiovascular strain, and RPE while it improved perceived recovery in catchers over a simulated 3-game series performed in hot conditions.

GRIPPING DEVICE FOR CYLINDRICAL OBJECTS

DOEpatents

Pilger, J.P.

1964-01-21

A gripping device is designed for fragile cylindrical objects such as for drawing thin-walled tubes. The gripping is done by multiple jaw members held in position by two sets of slots, one defined by keystone-shaped extensions of the outer shell of the device and the other in a movable sleeve held slidably by the extensions. Forward movement oi the sleeve advances the jaws, thereby exerting a controlled, radial pressure on the object being gripped. (AEC)

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

PubMed

Uppal, Surabhi; Jee, Youn Hee; Lightbourne, Marissa; Han, Joan C; Stratakis, Constantine A

2017-01-01

Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella. The patient was diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple endocrine stimulation tests revealed RCC and combined pituitary hormone deficiency (growth hormone deficiency, secondary adrenal insufficiency and central hypothyroidism) likely due to RCC. We report the first case in the literature of a girl with 48, XXXX and combined pituitary hormone deficiency due to Rathke's cyst.

What have we learned about GPER function in physiology and disease from knockout mice?

PubMed

Prossnitz, Eric R; Hathaway, Helen J

2015-09-01

Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and pathophysiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also demonstrated roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. Copyright © 2015. Published by Elsevier Ltd.

BDNF val66met polymorphism affects aging of multiple types of memory.

PubMed

Kennedy, Kristen M; Reese, Elizabeth D; Horn, Marci M; Sizemore, April N; Unni, Asha K; Meerbrey, Michael E; Kalich, Allan G; Rodrigue, Karen M

2015-07-01

The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (p<.07) toward poorer associative memory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). This article is part of a Special Issue entitled Memory & Aging. Copyright © 2014 Elsevier B.V. All rights reserved.

Multiple binding sites involved in the effect of choline esters on decarbamoylation of monomethylcarbamoyl- or dimethylcarbamoly-acetylcholinesterase.

PubMed Central

Sok, D E; Kim, Y B; Choi, S J; Jung, C H; Cha, S H

1994-01-01

Multiple binding sites for inhibitory choline esters in spontaneous decarbamoylation of dimethylcarbamoyl-acetylcholinesterase (AChE) were suggested from a wide range of IC50 values, in contrast with a limited range of AC50 values (concentration giving 50% of maximal activation) at a peripheral activatory site. Association of choline esters containing a long acyl chain (C7-C12) with the hydrophobic zone in the active site could be deduced from a linear relationship between the size of the acyl group and the inhibitory potency in either spontaneous decarbamoylation or acetylthiocholine hydrolysis. Direct support for laurylcholine binding to the active site might come from the competitive inhibition (Ki 33 microM) of choline-catalysed decarbamoylation by laurylcholine. Moreover, its inhibitory action was greater for monomethylcarbamoyl-AChE than for dimethylcarbamoyl-AChE, where there is a greater steric hindrance at the active centre. In further support, the inhibition of pentanoylthiocholine-induced decarbamoylation by laurylcholine was suggested to be due to laurylcholine binding to a central site rather than a peripheral site, similar to the inhibition of spontaneous decarbamoylation by laurylcholine. Supportive data for acetylcholine binding to the active site are provided by the results that acetylcholine is a competitive inhibitor (Ki 7.6 mM) of choline-catalysed decarbamoylation, and its inhibitory action was greater for monomethylcarbamoyl-AChE than for dimethylcarbamoyl-AChE. Meanwhile, choline esters with an acyl group of an intermediate size (C4-C6), more subject to steric exclusion at the active centre, and less associable with the hydrophobic zone, appear to bind preferentially to a peripheral activity site. Thus the multiple effects of choline esters may be governed by hydrophobicity and/or a steric effect exerted by the acyl moiety at the binding sites. PMID:8053896

The Protective Effect of Lidocaine on Septic Rats via the Inhibition of High Mobility Group Box 1 Expression and NF-κB Activation

PubMed Central

Wang, Huan-Liang; Xing, Yan-Qiu; Xu, Ying-Xue; Rong, Fei; Lei, Wei-Fu; Zhang, Wen-Hua

2013-01-01

Lidocaine, a common local anesthetic drug, has anti-inflammatory effects. It has demonstrated a protective effect in mice from septic peritonitis. However, it is unknown whether lidocaine has effects on high mobility group box 1 (HMGB1), a key mediator of inflammation. In this study, we investigated the effect of lidocaine treatment on serum HMGB1 level and HMGB1 expression in liver, lungs, kidneys, and ileum in septic rats induced by cecal ligation and puncture (CLP). We found that acute organ injury induced by CLP was mitigated by lidocaine treatment and organ function was significantly improved. The data also demonstrated that lidocaine treatment raised the survival of septic rats. Furthermore, lidocaine suppressed the level of serum HMGB1, the expression of HMGB1, and the activation of NF-κB p65 in liver, kidneys, lungs, and ileum. Taken together, these results suggest that lidocaine treatment exerts its protective effection on CLP-induced septic rats. The mechanism was relative to the inhibitory effect of lidocaine on the mRNA expression level of HMGB1 in multiple organs, release of HMGB1 to plasma, and activation of NF-κB. PMID:24371375

Exercise, physical activity, and exertion over the business cycle.

PubMed

Colman, Gregory; Dave, Dhaval

2013-09-01

Shifts in time and income constraints over economic expansions and contractions would be expected to affect individuals' behaviors. We explore the impact of the business cycle on individuals' exercise, time use, and total physical exertion, utilizing information on 112,000 individual records from the 2003-2010 American Time Use Surveys. In doing so, we test a key causal link that has been hypothesized in the relation between unemployment and health, but not heretofore assessed. Using more precise measures of exercise (and other activities) than previous studies, we find that as work-time decreases during a recession, recreational exercise, TV-watching, sleeping, childcare, and housework increase. This, however, does not compensate for the decrease in work-related exertion due to job-loss, and total physical exertion declines. These effects are strongest among low-educated men, which is validating given that employment in the Great Recession has declined most within manufacturing, mining, and construction. We also find evidence of intra-household spillover effects, wherein individuals respond to shifts in spousal employment conditional on their own labor supply. The decrease in total physical activity during recessions is especially problematic for vulnerable populations concentrated in boom-and-bust industries, and may have longer-term effects on obesity and related health outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

The obesogen tributyltin.

PubMed

Grün, Felix

2014-01-01

The obesogen hypothesis postulates the role of environmental chemical pollutants that disrupt homeostatic controls and adaptive mechanisms to promote adipose-dependent weight gain leading to obesity and metabolic syndrome complications. One of the most direct molecular mechanisms for coupling environmental chemical exposures to perturbed physiology invokes pollutants mimicking endogenous endocrine hormones or bioactive dietary signaling metabolites that serve as nuclear receptor ligands. The organotin pollutant tributyltin can exert toxicity through multiple mechanisms but most recently has been shown to bind, activate, and mediate RXR-PPARγ transcriptional regulation central to lipid metabolism and adipocyte biology. Data in support of long-term obesogenic effects on whole body adipose tissue are also reported. Organotins represent an important model test system for evaluating the impact and epidemiological significance of chemical insults as contributing factors for obesity and human metabolic health. © 2014 Elsevier Inc. All rights reserved.

How multiple causes combine: independence constraints on causal inference.

PubMed

Liljeholm, Mimi

2015-01-01

According to the causal power view, two core constraints-that causes occur independently (i.e., no confounding) and influence their effects independently-serve as boundary conditions for causal induction. This study investigated how violations of these constraints modulate uncertainty about the existence and strength of a causal relationship. Participants were presented with pairs of candidate causes that were either confounded or not, and that either interacted or exerted their influences independently. Consistent with the causal power view, uncertainty about the existence and strength of causal relationships was greater when causes were confounded or interacted than when unconfounded and acting independently. An elemental Bayesian causal model captured differences in uncertainty due to confounding but not those due to an interaction. Implications of distinct sources of uncertainty for the selection of contingency information and causal generalization are discussed.

Hydration and thermal strain during tennis in the heat.

PubMed

Bergeron, Michael F

2014-04-01

Competitive tennis in the heat can prompt substantial sweat losses and extensive consequent body water and electrolyte deficits, as well as a level of thermal strain that considerably challenges a player's physiology, perception of effort, and on-court well-being and performance. Adequate hydration and optimal performance can be notably difficult to maintain when multiple same-day matches are played on successive days in hot weather. Despite the recognised effects of the heat, much more research needs to be carried out to better appreciate the broader scope and full extent of the physiological demands and hydration and thermal strain challenges facing junior and adult players in various environments, venues and competition scenarios. However, certain recommendations of best practices should be emphasised to minimise exertional heat illness risk and improve player safety, well-being and on-court performance.

Sandalwood Album Oil as a Botanical Therapeutic in Dermatology.

PubMed

Moy, Ronald L; Levenson, Corey

2017-10-01

Many skin conditions and diseases are characterized by inflammation, infection, and hyperplasia. Safe and effective topical treatment options that can be used long-term are needed. Traditional botanical medicines, which are often complex mixtures that exert their biological activities via multiple mechanisms of action, are being studied as potential new active ingredients in dermatology. Sandalwood album oil (SAO), also known as East Indian sandalwood oil (EISO), is an essential oil distilled from the Santalum album tree and has demonstrated biological activity as an anti-inflammatory, anti-microbial, and anti-proliferative agent. Sandalwood album oil has also shown promise in clinical trials for treatment of acne, psoriasis, eczema, common warts, and molluscum contagiosum. The favorable safety profile, ease of topical use, and recent availability of pharmaceutical-grade sandalwood album oil support its broader use as the basis of novel therapies in dermatology.

A Negative Allosteric Modulator for α5 Subunit-Containing GABA Receptors Exerts a Rapid and Persistent Antidepressant-Like Action without the Side Effects of the NMDA Receptor Antagonist Ketamine in Mice

PubMed Central

Nelson, Mackenzie E.; Krimmel, Samuel R.; Georgiou, Polymnia; Gould, Todd D.

2017-01-01

Abstract New antidepressant pharmacotherapies that provide rapid relief of depressive symptoms are needed. The NMDA receptor antagonist ketamine exerts rapid antidepressant actions in depressed patients but also side effects that complicate its clinical utility. Ketamine promotes excitatory synaptic strength, likely by producing high-frequency correlated activity in mood-relevant regions of the forebrain. Negative allosteric modulators of GABA-A receptors containing α5 subunits (α5 GABA-NAMs) should also promote high-frequency correlated electroencephalogram (EEG) activity and should therefore exert rapid antidepressant responses. Because α5 subunits display a restricted expression in the forebrain, we predicted that α5 GABA-NAMs would produce activation of principle neurons but exert fewer side effects than ketamine. We tested this hypothesis in male mice and observed that the α5 GABA-NAM MRK-016 exerted an antidepressant-like response in the forced swim test at 1 and 24 h after administration and an anti-anhedonic response after chronic stress in the female urine sniffing test (FUST). Like ketamine, MRK-016 produced a transient increase in EEG γ power, and both the increase in γ power and its antidepressant effects in the forced swim test were blocked by prior administration of the AMPA-type glutamate receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX). Unlike ketamine, however, MRK-016 produced no impairment of rota-rod performance, no reduction of prepulse inhibition (PPI), no conditioned-place preference (CPP), and no change in locomotion. α5 GABA-NAMs, thus reproduce the rapid antidepressant-like actions of ketamine, perhaps via an AMPA receptor (AMPAR)-dependent increase in coherent neuronal activity, but display fewer potential negative side effects. These compounds thus demonstrate promise as clinically useful fast-acting antidepressants. PMID:28275719

Do 'mind over muscle' strategies work? Examining the effects of attentional association and dissociation on exertional, affective and physiological responses to exercise.

PubMed

Lind, Erik; Welch, Amy S; Ekkekakis, Panteleimon

2009-01-01

Despite the well established physical and psychological benefits derived from leading a physically active life, rates of sedentary behaviour remain high. Dropout and non-compliance are major contributors to the problem of physical inactivity. Perceptions of exertion, affective responses (e.g. displeasure or discomfort), and physiological stress could make the exercise experience aversive, particularly for beginners. Shifting one's attentional focus towards environmental stimuli (dissociation) instead of one's body (association) has been theorized to enhance psychological responses and attenuate physiological stress. Research evidence on the effectiveness of attentional focus strategies, however, has been perplexing, covering the entire gamut of possible outcomes (association and dissociation having been shown to be both effective and ineffective). This article examines the effects of manipulations of attentional focus on exertional and affective responses, as well as on exercise economy and tolerance. The possible roles of the characteristics of the exercise stimulus (intensity, duration) and the exercise participants, methodological issues, and limitations of experimental designs are discussed. In particular, the critical role of exercise intensity is emphasized. Dissociative strategies may be more effective in reducing perceptions of exertion and enhancing affective responses at low to moderate exercise intensities, but their effectiveness may be diminished at higher and near-maximal levels, at which physiological cues dominate. Conversely, associative strategies could enable the exerciser to regulate intensity to avoid injury or overexertion. Thus, depending on intensity, both strategies have a place in the 'toolbox' of the public health or exercise practitioner as methods of enhancing the exercise experience and promoting long-term compliance.

Usefulness of a Perceived Exertion Scale for Monitoring Exercise Intensity in Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Stanish, Heidi I.; Aucoin, Michael

2007-01-01

In order to gain physical fitness and health, exercise must be performed at a sufficient level of intensity. Exercise intensity can be monitored with rated perceived exertion (RPE) scales to promote safe and effective programming. The usefulness of the Children's OMNI Scale as a subjective measure of intensity for adults with intellectual…

Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.

PubMed

Itakura, Masanori; Nakajima, Hidemitsu; Semi, Yuko; Higashida, Shusaku; Azuma, Yasu-Taka; Takeuchi, Tadayoshi

2015-11-13

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

Naringenin is a novel inhibitor of Dictyostelium cell proliferation and cell migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russ, Misty; Martinez, Raquel; Ali, Hind

2006-06-23

Naringenin is a flavanone compound that alters critical cellular processes such as cell multiplication, glucose uptake, and mitochondrial activity. In this study, we used the social amoeba, Dictyostelium discoideum, as a model system for examining the cellular processes and signaling pathways affected by naringenin. We found that naringenin inhibited Dictyostelium cell division in a dose-dependent manner (IC{sub 5} {approx} 20 {mu}M). Assays of Dictyostelium chemotaxis and multicellular development revealed that naringenin possesses a previously unrecognized ability to suppress amoeboid cell motility. We also found that naringenin, which is known to inhibit phosphatidylinositol 3-kinase activity, had no apparent effect on phosphatidylinositolmore » 3,4,5-trisphosphate synthesis in live Dictyostelium cells; suggesting that this compound suppresses cell growth and migration via alternative signaling pathways. In another context, the discoveries described here highlight the value of using the Dictyostelium model system for identifying and characterizing the mechanisms by which naringenin, and related compounds, exert their effects on eukaryotic cells.« less

Potential applications of antimicrobial fatty acids in medicine, agriculture and other industries.

PubMed

Desbois, Andrew P

2012-08-01

The antimicrobial effects of free fatty acids are well recognised and these compounds can prevent the growth of or directly kill bacteria, fungi and other microbes by affecting multiple cellular targets, including the cell membrane and components found therein. Moreover, fatty acids exert detrimental effects on microbial pathogens by interfering with mechanisms of virulence, such as preventing biofilm formation and inhibiting the production of toxins and enzymes. The antimicrobial properties of free fatty acids can be exploited for the preservation of perishable products, such as food and cosmetics, and for the prevention and treatment of infections. These safe natural products are particularly useful in circumstances where antimicrobial activity is required but where the use of conventional antibiotics is undesirable or forbidden. This review focuses on the most promising prospects for exploiting the antimicrobial properties of free fatty acids for applications in various industries. The benefits of using fatty acids as antimicrobial agents are discussed and relevant recent patents are highlighted.

Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures

PubMed Central

Yoshino, Atsushi; Polouliakh, Natalia; Meguro, Akira; Takeuchi, Masaki; Kawagoe, Tatsukata; Mizuki, Nobuhisa

2016-01-01

Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients. PMID:27621603

Failure of dietary alpha-difluoromethylornithine to inhibit gastric carcinogenesis in rats after 8 weeks of treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.

PubMed

Tanakamaru, Z; Nishikawa, A; Furukawa, F; Imazawa, T; Lee, I S; Kasahara, K; Tanaka, T; Takahashi, M

1997-11-25

The modifying effects of alpha-difluoromethylomithine (DFMO) on glandular stomach carcinogenesis after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride were investigated in male outbred Wistar rats. Animals were simultaneously given MNNG solution (100 ppm) as their drinking water and diet supplemented with 10% sodium chloride for 8 weeks, and administered DFMO (dietary levels of 2000 ppm or 500 ppm) and tap water for the following 70 weeks. The DFMO treatment did not show any tendency to inhibit the development of gastric adenocarcinomas. The incidences and multiplicities of atypical hyperplasias in the glandular stomachs were also comparable in all groups of rats given MNNG/sodium chloride. Neither gastric carcinomas nor atypical hyperplasias were observed without the carcinogen treatment. Thus, DFMO did not exert any inhibitory effects when given during the post-initiation phase of two-stage glandular stomach carcinogenesis in rats initiated with MNNG and sodium chloride for 8 weeks.

Beyond the therapeutic shackles of the monoamines: New mechanisms in bipolar disorder biology.

PubMed

Data-Franco, João; Singh, Ajeet; Popovic, Dina; Ashton, Melanie; Berk, Michael; Vieta, Eduard; Figueira, M L; Dean, Olivia M

2017-01-04

Multiple novel biological mechanisms putatively involved in the etiology of bipolar disorders are being explored. These include oxidative stress, altered glutamatergic neurotransmission, mitochondrial dysfunction, inflammation, cell signaling, apoptosis and impaired neurogenesis. Important clinical translational potential exists for such mechanisms to help underpin development of novel therapeutics - much needed given limitations of current therapies. These new mechanisms also help improve our understanding of how current therapeutics might exert their effects. Lithium, for example, appears to have antioxidant, immunomodulatory, signaling, anti-apoptotic and neuroprotective properties. Similar properties have been attributed to other mood stabilizers such as valproate, lamotrigine, and quetiapine. Perhaps of greatest translational value has been the recognition of such mechanisms leading to the emergence of novel therapeutics for bipolar disorders. These include the antioxidant N-acetylcysteine, the anti-inflammatory celecoxib, and ketamine - with effects on the glutamatergic system and microglial inhibition. We review these novel mechanisms and emerging therapeutics, and comment on next steps in this space. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Endogenous Microbiota, Probiotics and Their Biological Products in Human Health

PubMed Central

Howarth, Gordon S.; Wang, Hanru

2013-01-01

Although gut diseases such as inflammatory bowel disease, mucositis and the alimentary cancers share similar pathogenetic features, further investigation is required into new treatment modalities. An imbalance in the gut microbiota, breached gut integrity, bacterial invasion, increased cell apoptosis to proliferation ratio, inflammation and impaired immunity may all contribute to their pathogenesis. Probiotics are defined as live bacteria, which when administered in sufficient amounts, exert beneficial effects to the gastrointestinal tract. More recently, probiotic-derived factors including proteins and other molecules released from living probiotics, have also been shown to exert beneficial properties. In this review we address the potential for probiotics, with an emphasis on probiotic-derived factors, to reduce the severity of digestive diseases and further discuss the known mechanisms by which probiotics and probiotic-derived factors exert their physiological effects. PMID:23306189

Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology

PubMed Central

Yohn, Samantha E.; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

2016-01-01

Abstract Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson’s disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision-making are highly translatable to humans, and an emerging body of evidence indicates that alterations in effort-based decision-making are evident in several psychiatric and neurological disorders. People with major depression, schizophrenia, and Parkinson’s disease show evidence of decision-making biases towards a lower exertion of effort. Translational studies linking research with animal models, human volunteers, and clinical populations are greatly expanding our knowledge about the neural basis of effort-related motivational dysfunction, and it is hoped that this research will ultimately lead to improved treatment for motivational and psychomotor symptoms in psychiatry and neurology. PMID:27189581

Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay.

PubMed

Salim, Elsayed I

2010-09-01

Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has been widely used for various medicinal and nutritional purposes. Volatile oil extracts along with its major constituents, such as thymoquinone, have recently attracted considerable attention for their antioxidant, immunoprotective and antitumor properties. The present study was conducted to assess the chemopreventive potential of crude oils in N. sativa on tumor formation using a well-established rat multi-organ carcinogenesis model featuring initial treatment with five different carcinogens. Post-initiation administration of 1000 or 4000 ppm N. sativa volatile oil in the diet of male Wistar rats for 30 weeks significantly reduced malignant and benign colon tumor sizes, incidences and multiplicities. The treatment also significantly decreased the incidences and multiplicities of tumors in the lungs and in different parts of the alimentary canal, particularly the esophagus and forestomach. Bromodeoxyuridine labeling indices, reflecting cell proliferation were significantly decreased in various organs and lesions after treatment with the two doses of N. sativa. The plasma levels of insulin growth factor, triglycerides and prostaglandin E2 were also altered. The findings show, for the first time, that N. sativa administration exerts potent inhibitory effects on rat tumor development and on cellular proliferation in multiple organ sites. In particular, the ability to significantly inhibit murine colon, lung, esophageal and forestomach tumors was demonstrated in the post-initiation phase, with no evidence of clinical side effects. The mechanisms are likely to be related to suppression of cell proliferation.

Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay

PubMed Central

SALIM, ELSAYED I.

2010-01-01

Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has been widely used for various medicinal and nutritional purposes. Volatile oil extracts along with its major constituents, such as thymoquinone, have recently attracted considerable attention for their antioxidant, immunoprotective and antitumor properties. The present study was conducted to assess the chemopreventive potential of crude oils in N. sativa on tumor formation using a well-established rat multi-organ carcinogenesis model featuring initial treatment with five different carcinogens. Post-initiation administration of 1000 or 4000 ppm N. sativa volatile oil in the diet of male Wistar rats for 30 weeks significantly reduced malignant and benign colon tumor sizes, incidences and multiplicities. The treatment also significantly decreased the incidences and multiplicities of tumors in the lungs and in different parts of the alimentary canal, particularly the esophagus and forestomach. Bromodeoxyuridine labeling indices, reflecting cell proliferation were significantly decreased in various organs and lesions after treatment with the two doses of N. sativa. The plasma levels of insulin growth factor, triglycerides and prostaglandin E2 were also altered. The findings show, for the first time, that N. sativa administration exerts potent inhibitory effects on rat tumor development and on cellular proliferation in multiple organ sites. In particular, the ability to significantly inhibit murine colon, lung, esophageal and forestomach tumors was demonstrated in the post-initiation phase, with no evidence of clinical side effects. The mechanisms are likely to be related to suppression of cell proliferation. PMID:22966405

Down-regulation of multiple low dose streptozotocin-induced diabetes by mycophenolate mofetil

PubMed Central

MAKSIMOVIC-IVANIC, D; TRAJKOVIC, V; MILJKOVIC, DJ; STOJKOVIC, M MOSTARICA; STOSIC-GRUJICIC, S

2002-01-01

The new immunosuppressive agent mycophenolate mofetil (MMF) has been shown recently to exert a protective effects in certain animal models of autoimmunity, including diabetes in diabetes-prone bio-breeding (BB) rats. In the present study, the immunomodulatory potential of MMF was investigated in autoimmune diabetes induced by multiple low doses of streptozotocin (MLD-STZ) in genetically susceptible DA rats 20 mg STZ/kg body weight (b.w.) for 5 days] and CBA/H mice (40 mg STZ/kg b.w. for 5 days). In both species, short time treatment of animals with MMF (25 mg/kg) during the early development of the disease, as well as continuous MMF treatment, prevented the appearance of hyperglycaemia and inflammatory infiltrates in the pancreatic tissue. Moreover, clinical manifestations of diabetes were suppressed by application of the drug after the onset of clinical symptoms. Treatment with guanosine (1 mg/kg) in parallel with MMF completely reversed MMF activity in vivo, indicating that inhibition of inosine monophosphate dehydrogenase (IMPDH) was responsible for the observed suppressive effects. MMF-mediated protection from diabetes correlated with reduced ex vivo spontaneous spleen mononuclear cell (MNC) proliferation and defective adhesive cell interactions. MMF-treated animals also had lower local production of IFN-γ, as well as IL-12 and nitric oxide (NO) production by peripheral tissues (spleen and peritoneal cells), compared to that in control diabetic groups, while IL-10 level was elevated. Together, these data demonstrate that MMF interferes with autoimmune process in streptozotocin-induced diabetes at multiple levels, including lymphocyte proliferation and adhesion, as well as pro/anti-inflammatory cytokine balance. PMID:12165076

Selective Control of Attention Supports the Positivity Effect in Aging

PubMed Central

Sasse, Laura K.; Gamer, Matthias; Büchel, Christian; Brassen, Stefanie

2014-01-01

There is emerging evidence for a positivity effect in healthy aging, which describes an age-specific increased focus on positive compared to negative information. Life-span researchers have attributed this effect to the selective allocation of cognitive resources in the service of prioritized emotional goals. We explored the basic principles of this assumption by assessing selective attention and memory for visual stimuli, differing in emotional content and self-relevance, in young and old participants. To specifically address the impact of cognitive control, voluntary attentional selection during the presentation of multiple-item displays was analyzed and linked to participants' general ability of cognitive control. Results revealed a positivity effect in older adults' selective attention and memory, which was particularly pronounced for self-relevant stimuli. Focusing on positive and ignoring negative information was most evident in older participants with a generally higher ability to exert top-down control during visual search. Our findings highlight the role of controlled selectivity in the occurrence of a positivity effect in aging. Since the effect has been related to well-being in later life, we suggest that the ability to selectively allocate top-down control might represent a resilience factor for emotional health in aging. PMID:25093459

From Animal House to Old School: a multiple mediation analysis of the association between college drinking movie exposure and freshman drinking and its consequences.

PubMed

Osberg, Timothy M; Billingsley, Katherine; Eggert, Meredith; Insana, Maribeth

2012-08-01

Does exposure to college drinking movies impact upon subsequent college student drinking? If so, what mechanisms mediate such an effect? In the first study to address these questions, we assessed college drinking movie exposure in a sample of 479 college freshmen early in their first semester and examined its relation to subsequent drinking and drinking consequences one month later. Hypothesized mediators of this effect included college alcohol beliefs (beliefs that drinking is central to college life), positive and negative alcohol expectancies, and descriptive and injunctive norms. Using bootstrapping procedures, results indicated that movie exposure exerted direct effects on both drinking and drinking consequences. Movie exposure also had significant indirect effects on drinking through all of the hypothesized mediators, with the exception of negative alcohol expectancies. All mediated movie exposure's effects on drinking consequences, with the exception of injunctive norms. Contrast analyses revealed that college alcohol beliefs had the strongest mediational effects in the relationship between movie exposure and both drinking and consequences. The implications of these findings for precollege alcohol education programs are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Selective control of attention supports the positivity effect in aging.

PubMed

Sasse, Laura K; Gamer, Matthias; Büchel, Christian; Brassen, Stefanie

2014-01-01

There is emerging evidence for a positivity effect in healthy aging, which describes an age-specific increased focus on positive compared to negative information. Life-span researchers have attributed this effect to the selective allocation of cognitive resources in the service of prioritized emotional goals. We explored the basic principles of this assumption by assessing selective attention and memory for visual stimuli, differing in emotional content and self-relevance, in young and old participants. To specifically address the impact of cognitive control, voluntary attentional selection during the presentation of multiple-item displays was analyzed and linked to participants' general ability of cognitive control. Results revealed a positivity effect in older adults' selective attention and memory, which was particularly pronounced for self-relevant stimuli. Focusing on positive and ignoring negative information was most evident in older participants with a generally higher ability to exert top-down control during visual search. Our findings highlight the role of controlled selectivity in the occurrence of a positivity effect in aging. Since the effect has been related to well-being in later life, we suggest that the ability to selectively allocate top-down control might represent a resilience factor for emotional health in aging.

Effects of natalizumab treatment on Foxp3+ T regulatory cells.

PubMed

Stenner, Max-Philipp; Waschbisch, Anne; Buck, Dorothea; Doerck, Sebastian; Einsele, Hermann; Toyka, Klaus V; Wiendl, Heinz

2008-10-06

Natalizumab, a monoclonal humanized antibody targeting the alpha-4 chain of very late activation antigen 4 (VLA-4) exerts impressive therapeutic effects in patients with relapsing-remitting multiple sclerosis. Our objective was to study impacts of Natalizumab therapy on Foxp3+ T regulatory cells (Tregs) in multiple sclerosis (MS) patients. A combined approach of in vitro and ex vivo experiments using T cells isolated from the peripheral blood of healthy donors and Natalizumab treated MS patients was chosen. We determined binding of Natalizumab and its effects on the frequency, transmigratory behaviour and suppressive function of Tregs. Binding of Natalizumab and expression of CD49d (alpha-4 chain of VLA-4) differed between non-regulatory and regulatory cells. Albeit Foxp3+ Tregs had lower levels of CD49d, Natalizumab blocked the transmigration of Foxp3+ Tregs similar to non-regulatory T cells. The frequency of peripheral blood Tregs was unaffected by Natalizumab treatment. Natalizumab does not alter the suppressive capacity of CD4+CD25(high)CD127(low)Foxp3+ Tregs under in vitro conditions. Furthermore, the impaired function of Tregs in MS patients is not restored by Natalizumab treatment. We provide a first detailed analysis of Natalizumab effects on the regulatory T cell population. Our prospective study shows that Foxp3+ Tregs express lower levels of VLA-4 and bind less Natalizumab. We further the understanding of the mechanisms of action of Natalizumab by demonstrating that unlike other immunomodulatory drugs the beneficial therapeutic effects of the monoclonal antibody are largely independent of alterations in Treg frequency or function.

Effects of Natalizumab Treatment on Foxp3+ T Regulatory Cells

PubMed Central

Buck, Dorothea; Doerck, Sebastian; Einsele, Hermann; Toyka, Klaus V.; Wiendl, Heinz

2008-01-01

Background Natalizumab, a monoclonal humanized antibody targeting the alpha-4 chain of very late activation antigen 4 (VLA-4) exerts impressive therapeutic effects in patients with relapsing-remitting multiple sclerosis. Our objective was to study impacts of Natalizumab therapy on Foxp3+ T regulatory cells (Tregs) in multiple sclerosis (MS) patients. Methodology A combined approach of in vitro and ex vivo experiments using T cells isolated from the peripheral blood of healthy donors and Natalizumab treated MS patients was chosen. We determined binding of Natalizumab and its effects on the frequency, transmigratory behaviour and suppressive function of Tregs. Principal Findings Binding of Natalizumab and expression of CD49d (alpha-4 chain of VLA-4) differed between non-regulatory and regulatory cells. Albeit Foxp3+ Tregs had lower levels of CD49d, Natalizumab blocked the transmigration of Foxp3+ Tregs similar to non-regulatory T cells. The frequency of peripheral blood Tregs was unaffected by Natalizumab treatment. Natalizumab does not alter the suppressive capacity of CD4+CD25highCD127lowFoxp3+ Tregs under in vitro conditions. Furthermore, the impaired function of Tregs in MS patients is not restored by Natalizumab treatment. Conclusions We provide a first detailed analysis of Natalizumab effects on the regulatory T cell population. Our prospective study shows that Foxp3+ Tregs express lower levels of VLA-4 and bind less Natalizumab. We further the understanding of the mechanisms of action of Natalizumab by demonstrating that unlike other immunomodulatory drugs the beneficial therapeutic effects of the monoclonal antibody are largely independent of alterations in Treg frequency or function. PMID:18836525

An in vitro and in vivo study of a 4-herb formula on the management of diet-induced metabolic syndrome.

PubMed

Wat, Elaine; Wang, Yanping; Chan, Ken; Law, Hon Wai; Koon, Chi Man; Lau, Kit Man; Leung, Ping Chung; Yan, Choly; Lau, Clara Bik San

2018-03-15

Metabolic syndrome is the cluster of risk factors that leads to increased episodes of cardiovascular disease (CVD). These risk factors include but are not limited to obesity, non-alcoholic fatty liver (NAFLD), dyslipidemia, and type 2 diabetes. Since the pathogenesis of metabolic syndrome has multiple metabolic origins, there is no single treatment for it. Pharmacological approaches consist of separate drugs which target at individual risk factors which pose various side effects. Functional foods or nutraceuticals which have potentially important anti-obesity properties have thus attracted great attention. Schisandrae Fructus is a Chinese herb traditionally used as a liver tonic. Silymarin, an extract of the milk thistle (Silybum marianum), is a dietary supplement that is widely used in western society for the prevention and treatment of liver problems. Crataegus Fructus (hawthorn) is traditionally used to promote digestion and dissipate food stagnation. Momordica charantia (bitter melon) is traditionally used for treatment of diabetes in Ayurvedic Medicine. We aimed to develop a multi-targeted herbal formula to target on the multiple risk factors of metabolic syndrome using individual herbs. This proposed herbal formula include sylimarin and Schisandrae Fructus, for NAFLD; Crataegus Fructus for obesity and hyperlipidemia; and Momordica charantia for hyperglycemia. For in vitro study, we carried out insulin-induced 3T3-L1 adipocytes differentiation and fluorescent tagged cholesterol-treated Caco-2 cell assay to study for adipogenesis and cholesterol uptake into Caco-2 cells, respectively. Oleic acid-induced HepG2 cell assay was used to study for oleic acid-induced fatty liver, and brush border membrane vesicles (BBMV) assay was used to study for glucose uptake from the gut. For in vivo study, we performed an 8-week and a 12-week treatment studies, with each study comprising of 4 groups of C57Bl/6 male mice given: (i) Normal-chow diet; (ii)-(iv) High-fat diet (contains 21% fat and 0.15% cholesterol). After the initial 8 weeks of normal chow or high-fat diet feeding to induce obesity, animals were given: (i) Normal-chow diet; (ii) High-fat diet; (iii) High-fat diet + 2% herbal formula; or (iv) High-fat diet + 4% herbal formula as treatment for another 8 weeks or 12 weeks. Our in vitro results suggested Crataegus Fructus aqueous extract exerted potent inhibitory effects on 3T3-L1 preadipocytes differentiation and cholesterol uptake into Caco-2 cells. Schisandrae Fructus aqueous extract and milk thistle exerted inhibitory effects on oleic acid-induced fatty liver in HepG2 cells. Momordica charantia extract on the other hand, exerted significant inhibitory effect on glucose uptake into BBMV. Our in vivo results showed that our herbal formula exhibited a trend to reduce diet-induced increase in body weight and fat pad mass (epididymal, perirenal and inguinal fat); and significantly reduced diet-induced increase in liver weight, liver lipid, and plasma lipid dose-dependently. Besides, high-fat diet induced a significant reduction in adiponectin level which was significantly improved by herbal formula supplementation at 4%. There was however no significant effect of the herbal formula on diet-induced increase in plasma glucose or insulin levels at either dose. Herbal formula also significantly reduced diet-induced inflammation in the liver at both doses. Taken together, these data suggested the potential of our novel multi-targeted herbal formula to be used as a therapeutic agent for diet-induced metabolic syndrome, with special emphasis on NAFLD. Copyright © 2018. Published by Elsevier GmbH.

Racial disparities in age at time of homicide victimization: a test of the multiple disadvantage model.

PubMed

Lo, Celia C; Howell, Rebecca J; Cheng, Tyrone C

2015-01-01

This study sought the factors associated with race/ethnicity disparities in the age at which homicide deaths tend to occur. We used the multiple disadvantage model to take race into account as we evaluated associations between age at time of homicide victimization and several social structural, mental health-related, and lifestyle factors. Data were derived from the 1993 National Mortality Followback Survey, a cross-sectional interview study of spouses, next of kin, other relatives, and close friends of individuals 15 years and older who died in the United States in 1993. Our results showed age at time of homicide mortality to be related to the three types of factors; race moderated some of these relationships. In general, being employed, married, and a homeowner appeared associated with reduced victimization while young. The relationship of victimization age and employment was not uniform across racial groups, nor was the relationship of victimization age and marital status uniform across groups. Among Blacks, using mental health services was associated with longer life. Homicide by firearm proved important for our Black and Hispanic subsamples, while among Whites, alcohol's involvement in homicide exerted significant effects. Our results suggest that programs and policies serving the various racial/ethnic groups can alleviate multiple disadvantages relevant in homicide victimization at an early age. © The Author(s) 2014.

Full-Scale Instrumented Evaluations of Multiple Airfield Matting Systems on Soft Soil to Characterize Permanent Deformation

DTIC Science & Technology

2016-06-01

Development of a new design methodology for structural airfield mats. International Journal of Pavement Research and Tech- nology 3(3):102-109...load exerted by aircraft over a larger area. Six airfield matting systems of varying materials and designs were evaluated through the construction...position unless so designated by other authorized documents. DESTROY THIS REPORT WHEN NO LONGER NEEDED. DO NOT RETURN IT TO THE ORIGINATOR. ERDC/GSL

Prunus mume extract exerts antioxidant activities and suppressive effect of melanogenesis under the stimulation by alpha-melanocyte stimulating hormone in B16-F10 melanoma cells.

PubMed

Pi, KyungBae; Lee, KiBeom

2017-10-01

In the current study, we examined the antioxidant and skin-whitening properties of Prunus mume extract (PME). The ability of PME to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals was investigated in vitro. At a concentration of 1000 μg/mL, PME neutralized >45% free radical activity. Cell viability assessment with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that at concentrations <1500 μg/mL, PME does not exert cytotoxic effects on murine B16 melanoma (B16) cells. Morphological analysis disclosed that melanin production is inhibited in B16 cells treated with 250 nM α-melanocyte-stimulating hormone (α-MSH) and PME. We conclude that fruit extracts of P. mume exert a skin-whitening effect by inhibiting melanin production via regulation of melanogenesis-associated protein expression in melanocytes.

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

PubMed

Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

2013-12-01

Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital. Postnatal day (P)7 rats were treated with phenobarbital (0-40mg/kg) and/or melatonin (0-80mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats

PubMed Central

Forcelli, Patrick A.; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

2013-01-01

Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital, the most commonly utilized anticonvulsant in neonatal medicine. Postnatal day (P)7 rats were treated with phenobarbital (0–40 mg/kg) and/or melatonin (0–80 mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100 mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. PMID:24206906

Interest Group Conflict Over Medicaid Expansion: The Surprising Impact of Public Advocates.

PubMed

Callaghan, Timothy; Jacobs, Lawrence R

2016-02-01

We examined the potential economic, policy, and political influences on the decisions of the 50 US states to expand Medicaid under the Affordable Care Act. We related a measure of relative state progress toward Medicaid expansion updated to 2015 to each state's economic circumstances, established policy frameworks in states, partisan control of state government, and lobbyists for businesses, medical professionals, unions, and public interest organizations. The 9201 lobbyists working on health care reform in state capitols exerted a strong and significant impact on Medicaid expansion. Controlling for confounding factors (including partisanship and existing policy frameworks), we found that business and professional lobbyists exerted a negative effect on state Medicaid expansion and, unexpectedly, that public interest advocates exerted a positive effect. There are 3.1 million adults who lack coverage because they live in the 20 states that refused to expand Medicaid. Although political party and lobbyists for private interests present significant barriers in these states, legislative lobbying on behalf of the uninsured appears likely to be effective.

Neurohumoral improvement and torsional dynamics in patients with heart failure after treatment with levosimendan.

PubMed

Navarri, Romina; Lunghetti, Stefano; Cameli, Matteo; Mondillo, Sergio; Favilli, Roberto; Scarpini, Francesca; Puccetti, Luca

2015-06-01

Levosimendan improves clinical and hemodynamic parameters exerting an anti-inflammatory and antiapoptotic effect in decompensated heart failure. The aim of this study was to evaluate the effects of levosimendan on LV torsion, plasma levels of NT-proBNP and on the balance between pro-inflammatory (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10). We enrolled 24 patients (age 62 ± 7 years) with acute HF, NYHA class IV and severe LV dysfunction. All patients underwent transthoracic echocardiography using two-dimensional speckle tracking analysis to detect LV twist angle (LVTA), at baseline and 1 week after treatment with levosimendan infusion. Biochemical parameters (pro-BNP, IL-6, IL-10, TNF-α) were determined by enzyme-linked immunosorbent (ELISA). After one week, we observed an improvement in LV function especially in LVTA (4.15 ± 2.54 vs 2.9 ± 2.1 p < 0.01), in LV ejection fraction (27.3 ± 8.04 vs 21.6 ± 6.8 p = 0.03) and also a significant reduction in BNP levels (1844 ± 560 vs 4713 ± 1050, p = 0.03). The multiple linear regression analysis showed a significant relation between a reduction of TNF α/IL-10 ratio (Δ > 20%) and BNP (Δ > 40%), LVEF (Δ > 10%) and LVTA (Δ > 20%) (O.R. 1.77, 95% C.I. 1.11-2.83; O.R. 1.49, 95% C.I. 1.08-2.67; O.R. 1.66, 95% C.I. 1.10-2.74, respectively, confirmed p, all < 0.01 by Hosmer-Lemeshov confirmation and the formal test for interaction). Levosimendan exerts a hemodynamic effect by improving EF and LV torsion in patients with acute HF in association with a positive effect on the balance between pro and anti-inflammatory cytokines.

Gamma-hydroxybutyric acid (GHB) and the mesoaccumbens reward circuit: evidence for GABA(B) receptor-mediated effects.

PubMed

Pistis, M; Muntoni, A L; Pillolla, G; Perra, S; Cignarella, G; Melis, M; Gessa, G L

2005-01-01

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid naturally occurring in the mammalian brain, which recently emerged as a major recreational drug of abuse. GHB has multiple neuronal mechanisms including activation of both the GABA(B) receptor, and a distinct GHB-specific receptor. This complex GHB-GABA(B) receptor interaction is probably responsible for the multifaceted pharmacological, behavioral and toxicological profile of GHB. Drugs of abuse exert remarkably similar effects upon reward-related circuits, in particular the mesolimbic dopaminergic system and the nucleus accumbens (NAc). We used single unit recordings in vivo from urethane-anesthetized rats to characterize the effects of GHB on evoked firing in NAc "shell" neurons and on spontaneous activity of antidromically identified dopamine (DA) cells located in the ventral tegmental area. GHB was studied in comparison with the GABA(B) receptor agonist baclofen and antagonist (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911). Additionally, we utilized a GHB analog, gamma-(p-methoxybenzil)-gamma-hydroxybutyric acid (NCS-435), devoid of GABA(B) binding properties, but with high affinity for specific GHB binding sites. In common with other drugs of abuse, GHB depressed firing in NAc neurons evoked by the stimulation of the basolateral amygdala. On DA neurons, GHB exerted heterogeneous effects, which were correlated to the baseline firing rate of the cells but led to a moderate stimulation of the DA system. All GHB actions were mediated by GABA(B) receptors, since they were blocked by SCH50911 and were not mimicked by NCS-435. Our study indicates that the electrophysiological profile of GHB is close to typical drugs of abuse: both inhibition of NAc neurons and moderate to strong stimulation of DA transmission are distinctive features of diverse classes of abused drugs. Moreover, it is concluded that addictive and rewarding properties of GHB do not necessarily involve a putative high affinity GHB receptor.

The relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of non-melanoma skin cancer (NMSC)

PubMed Central

Reichrath, Jörg; Reichrath, Sandra

2013-01-01

Solar UV (UV)-B-radiation exerts both beneficial and adverse effects on human health. On the one hand, it is the most important environmental risk factor for the development of non-melanoma skin cancer [NMSC; most importantly basal (BCC) and squamous (SCC) cell carcinomas], that represent the most common malignancies in Caucasian populations. On the other hand, the human body’s requirements of vitamin D are mainly achieved by UV-B-induced cutaneous photosynthesis. This dilemma represents a serious problem in many populations, for an association of vitamin D-deficiency and multiple independent diseases including various types of cancer has been convincingly demonstrated. In line with these findings, epidemiologic and laboratory investigations now indicate that vitamin D and its metabolites have a risk reducing effect for NMSC. Potential mechanisms of action include inhibition of the hedgehog signaling pathway (BCC) and modulation of p53-mediated DNA damage response (SCC). As a consequence of these new findings it can be concluded that UV-B-radiation exerts both beneficial and adverse effects on risk and prognosis of NMSC. It can be assumed that many independent factors, including frequency and dose of UV-B exposure, skin area exposed, and individual factors (such as skin type and genetic determinants of the skin`s vitamin D status and of signaling pathways that are involved in the tumorigenesis of NMSC) determine whether UV-B exposure promotes or inhibits tumorigenesis of NMSC. Moreover, these findings may help to explain many of the differential effects of UV-B radiation on risk of NMSC, including variation in the dose-dependent risk for development of SCC in situ (actinic keratosis, AK), invasive SCC, and BCC. In this review, we analyze the relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of NMSC and give an overview of present concepts and future perspectives. PMID:24494041

Multiple regulation by external ATP of nifedipine-insensitive, high voltage-activated Ca(2+) current in guinea-pig mesenteric terminal arteriole.

PubMed

Morita, Hiromitsu; Sharada, Thapaliya; Takewaki, Tadashi; Ito, Yushi; Inoue, Ryuji

2002-03-15

We investigated the receptor-mediated regulation of nifedipine-insensitive, high voltage-activated Ca(2+) currents in guinea-pig terminal mesenteric arterioles (I(mVDCC)) using the whole-cell clamp technique. Screening of various vasoactive substances revealed that ATP, histamine and substance P exert modulatory effects on I(mVDCC). The effects of ATP on I(mVDCC) after complete P2X receptor desensitization exhibited a complex concentration dependence. With 5 mM Ba(2+), ATP potentiated I(mVDCC) at low concentrations (approximately 1-100 microM), but inhibited it at higher concentrations (>100 microM). The potentiating effects of ATP were abolished by suramin (100 microM) and PPADS (10 microM) and by intracellular application of GDPbetaS (500 microM), whereas a substantial part of I(mVDCC) inhibition by milimolar concentrations of ATP remained unaffected; due probably to its divalent cation chelating actions. In divalent cation-free solution, I(mVDCC) was enlarged and underwent biphasic effects by ATPgammaS and ADP, while 2-methylthio ATP (2MeSATP) exerted only inhibition, and pyrimidines such as UTP and UDP were ineffective. ATP-induced I(mVDCC) potentiation was selectively inhibited by anti-Galpha(s) antibodies or protein kinase A (PKA) inhibitory peptides and mimicked by dibutyryl cAMP. In contrast, ATP-induced inhibition was selectively inhibited by Galpha(q/11) antibodies or protein kinase C (PKC) inhibitory peptides and mimicked by PDBu. Pretreatment with pertussis toxin was ineffective. The apparent efficacy for I(mVDCC) potentiation with PKC inhibitors was: ATPgammaS > ATP>/=ADP and for inhibition with PKA inhibitors was: 2MeSATP > ATPgammaS > ATP > ADP. Neither I(mVDCC) potentiation nor inhibition showed voltage dependence. These results suggest that I(mVDCC) is multi-phasically regulated by external ATP via P2Y(11)-resembling receptor/G(s)/PKA pathway, P2Y(1)-like receptor/G(q/11)/PKC pathway, and metal chelation.

New weight factor for Brownian force exerted on micro/nano-particles in air flow

NASA Astrophysics Data System (ADS)

Zhang, Peijie; Lin, Jianzhong; Ku, Xiaoke

2018-05-01

In order to effectively describe the effect of Brownian force exerted on the micro/nano-particles in air flow, a new weight factor, which is defined as the ratio of the characteristic velocity of the Brownian motion to the macroscopic velocity, is proposed and applied to the particle settlement under gravity. Results show that the weight factor can quantitatively evaluate the effect of Brownian force on the particle motion. Moreover, the value of the weight factor can also be used to judge the particle motion pattern and determine whether the Brownian force should be taken into account.

Independently evolved upper jaw protrusion mechanisms show convergent hydrodynamic function in teleost fishes.

PubMed

Staab, Katie Lynn; Holzman, Roi; Hernandez, L Patricia; Wainwright, Peter C

2012-05-01

A protrusible upper jaw has independently evolved multiple times within teleosts and has been implicated in the success of two groups in particular: Acanthomorpha and Cypriniformes. We use digital particle image velocimetry (DPIV) to compare suction feeding flow dynamics in a representative of each of these clades: goldfish and bluegill. Using DPIV, we contrast the spatial pattern of flow, the temporal relationship between flow and head kinematics, and the contribution of jaw protrusion to the forces exerted on prey. As expected, the spatial patterns of flow were similar in the two species. However, goldfish were slower to reach maximal kinematic excursions, and were more flexible in the relative timing of jaw protrusion, other jaw movements and suction flows. Goldfish were also able to sustain flow speeds for a prolonged period of time as compared with bluegill, in part because goldfish generate lower peak flow speeds. In both species, jaw protrusion increased the force exerted on the prey. However, slower jaw protrusion in goldfish resulted in less augmentation of suction forces. This difference in force exerted on prey corresponds with differences in trophic niches and feeding behavior of the two species. The bluegill uses powerful suction to capture insect larvae whereas the goldfish uses winnowing to sort through detritus and sediment. The kinethmoid of goldfish may permit jaw protrusion that is independent of lower jaw movement, which could explain the ability of goldfish to decouple suction flows (due to buccal expansion) from upper jaw protrusion. Nevertheless, our results show that jaw protrusion allows both species to augment the force exerted on prey, suggesting that this is a fundamental benefit of jaw protrusion to suction feeders.

N-ω-chloroacetyl-L-ornithine has in-vitro activity against cancer cell lines and in-vivo activity against ascitic and solid tumors.

PubMed

Vargas-Ramírez, Alba L; Medina-Enríquez, Miriam M; Cordero-Rodríguez, Neira I; Ruiz-Cuello, Tatiana; Aguilar-Faisal, Leopoldo; Trujillo-Ferrara, José G; Alcántara-Farfán, Verónica; Rodríguez-Páez, Lorena

2016-07-01

N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.

Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corona, Giulia; Dipartimento di Biologia Sperimentale, Sez. Patologia Sperimentale, Universita degli Studi di Cagliari, 09042 Monserrato; Deiana, Monica

2007-10-26

We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 {mu}g/ml) the number of cells in the G2/M phase increased to 51.82 {+-} 2.69% relative to control cells (15.1 {+-} 2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 {mu}g/ml) to exert rapid inhibitionmore » of p38 (38.7 {+-} 4.7%) and CREB (28.6 {+-} 5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9 {+-} 9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development.« less

Policy statement—Climatic heat stress and exercising children and adolescents.

PubMed

Bergeron, Michael F; Devore, Cynthia; Rice, Stephen G

2011-09-01

Results of new research indicate that, contrary to previous thinking, youth do not have less effective thermoregulatory ability, insufficient cardiovascular capacity, or lower physical exertion tolerance compared with adults during exercise in the heat when adequate hydration is maintained. Accordingly, besides poor hydration status, the primary determinants of reduced performance and exertional heat-illness risk in youth during sports and other physical activities in a hot environment include undue physical exertion, insufficient recovery between repeated exercise bouts or closely scheduled same-day training sessions or rounds of sports competition, and inappropriately wearing clothing, uniforms, and protective equipment that play a role in excessive heat retention. Because these known contributing risk factors are modifiable, exertional heat illness is usually preventable. With appropriate preparation, modifications, and monitoring, most healthy children and adolescents can safely participate in outdoor sports and other physical activities through a wide range of challenging warm to hot climatic conditions.

Parent-Child Attunement Moderates the Prospective Link between Parental Overcontrol and Adolescent Adjustment.

PubMed

Miller, Kelly F; Borelli, Jessica L; Margolin, Gayla

2017-10-22

Parental overcontrol (OC), behavior that intrusively or dominantly restricts child autonomy, has been identified as a transdiagnostic risk factor for youth. However, it is as yet unknown whether the association between parental OC and child maladjustment remains even when OC is exerted infrequently or by attuned parents. Rather, the selective use of OC might steer children away from danger. Taking a developmental psychopathology approach, this study focuses on the larger parent-child relationship context, testing whether either the dose at which parents demonstrate OC or the degree to which children perceive their parents as attuned determines whether OC is risky or protective for adolescents' adjustment. Among a community sample of 114 families of children followed from the ages of 12-18, we examine whether OC, behaviorally coded from triadic mother-father-child discussions in middle childhood, is associated with later risky behavior and anxiety symptoms in adolescence. Overcontrol exerted by either mothers or fathers had a curvilinear effect on adolescent risky behaviors, and this effect was moderated by children's perceived attunement. Although OC generally was associated with increased risky behaviors, low doses of OC or OC exerted by highly attuned parents protected against engagement in risky behaviors. No main effect of OC was observed on adolescent anxiety; however, mothers' OC interacted with perceived parental attunement, such that OC exerted by less attuned parents predicted greater anxiety. Results underscore that the effect of parenting behaviors depends on the larger parent-child relationship context. © 2017 Family Process Institute.

[Advances in novel carrier systems of chemical constituents from spice volatile oils].

PubMed

Zhang, Jia-jia; Zhu, Yuan; Yu, Jiang-nan; Xu, Xi-ming

2015-10-01

Recent years, chemical constituents from spice volatile oils have gained worldwide concern owing to its multiple pharmacological effects and safety for using as the natural antibacterial agents. However, their poor dissolution, strong volatility, serious irritation, weak stability, easy oxidation and low bioavailability characteristics are the major obstacle in the preparation of effective oral formulation and practical application. Therefore, there is an urgent need to select a novel carrier system that can delivery the chemical constituents from spice volatile oils more efficiently with improving their stability as well as alleviating the irritation, and develop the functional food, health products and even medicine for exerting their pharmacological effects, which also is the focus and nodus of the research on their application. This review presents recent systematic studies on their novel carrier systems, including cyclodextrin inclusion complex, liposomes, nanoemulsions, nanoparticles, solid dispersion and so on, and summarizes the characteristics, application range and problems of each novel carrier systems, in order to provide some beneficial thoughts in further developing new products of chemical constituents from spice volatile oils.

Variation in Indole-3-Acetic Acid Production by Wild Saccharomyces cerevisiae and S. paradoxus Strains from Diverse Ecological Sources and Its Effect on Growth

PubMed Central

Liu, Yen-Yu; Chen, Hung-Wei; Chou, Jui-Yu

2016-01-01

Phytohormone indole-3-acetic acid (IAA) is the most common naturally occurring and most thoroughly studied plant growth regulator. Microbial synthesis of IAA has long been known. Microbial IAA biosynthesis has been proposed as possibly occurring through multiple pathways, as has been proven in plants. However, the biosynthetic pathways of IAA and the ecological roles of IAA in yeast have not been widely studied. In this study, we investigated the variation in IAA production and its effect on the growth of Saccharomyces cerevisiae and its closest relative Saccharomyces paradoxus yeasts from diverse ecological sources. We found that almost all Saccharomyces yeasts produced IAA when cultured in medium supplemented with the primary precursor of IAA, L-tryptophan (L-Trp). However, when cultured in medium without L-Trp, IAA production was only detected in three strains. Furthermore, exogenous added IAA exerted stimulatory and inhibitory effects on yeast growth. Interestingly, a negative correlation was observed between the amount of IAA production in the yeast cultures and the IAA inhibition ratio of their growth. PMID:27483373

REGULATION OF MEMORY – FROM THE ADRENAL MEDULLA TO LIVER TO ASTROCYTES TO NEURONS1

PubMed Central

Gold, Paul E.

2014-01-01

Epinephrine, released into blood from the adrenal medulla in response to arousing experiences, is a potent enhancer of learning and memory processing. This review examines mechanisms by which epinephrine exerts its effects on these cognitive functions. Because epinephrine is largely blocked from moving from blood to brain, it is likely that the hormone's effects on memory are mediated by peripheral actions. A classic effect of epinephrine is to act at the liver to break down glycogen stores, resulting in increased blood glucose levels. The increase in blood glucose provides additional energy substrates to the brain to buttress the processes needed for an experience to be learned and remembered. In part, it appears that the increased glucose may act in the brain in a manner akin to that evident in the liver, engaging glycogenolysis in astrocytes to provide an energy substrate, in this case lactate, to augment neuronal functions. Together, the findings reveal a mechanism underlying modulation of memory that integrates the physiological functions of multiple organ systems to support brain processes. PMID:24406469

Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of T cell costimulatory molecules: Direct effect of Vpr on T cell activation and immune function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venkatachari, Narasimhan J.; Majumder, Biswanath; Ayyavoo, Velpandi

2007-02-20

Human immunodeficiency virus type 1 (HIV-1) viral proteins disrupt the normal host cellular immune pathways thus exploiting the cellular machinery for replication, survival and to escape host immune attack. Here we evaluated the direct effects of HIV-1 Vpr-mediated immune modulation of infected T cells. Vpr specifically downregulated the expression of CD28 and increased the expression of CTLA-4, whereas no significant difference in the expression of CD25 and HLA-DR was observed. Interferon gamma (IFN-{gamma}) production in T cells was evaluated as a measure of the downstream effector functions. Results indicate that Vpr significantly inhibited IFN-{gamma} production and this may, in part,more » due to Vpr's ability to inhibit the nuclear translocation of NF-{kappa}B, and its transcriptional regulation. Together these results support that HIV-1 Vpr selectively dysregulates the immune functions at multiple levels and exerts its inhibitory effects in the presence of other viral proteins.« less

From BACE1 Inhibitor to Multifunctionality of Tryptoline and Tryptamine Triazole Derivatives for Alzheimer’s Disease

PubMed Central

Jiaranaikulwanitch, Jutamas; Govitrapong, Piyarat; Fokin, Valery V.; Vajragupta, Opa

2013-01-01

Efforts to discover new drugs for Alzheimer’s disease emphasizing multiple targets was conducted seeking to inhibit amyloid oligomer formation and to prevent radical formation. The tryptoline and tryptamine cores of BACE1 inhibitors previously identified by virtual screening were modified in silico for additional modes of action. These core structures were readily linked to different side chains using 1,2,3-triazole rings as bridges by copper catalyzed azide-alkyne cycloaddition reactions. Three compounds among the sixteen designed compounds exerted multifunctional activities including β-secretase inhibitory action, anti-amyloid aggregation, metal chelating and antioxidant effects at micromolar levels. The neuroprotective effects of the multifunctional compounds 6h, 12c and 12h on Aβ1–42 induced neuronal cell death at 1 μM were significantly greater than those of the potent single target compound, BACE1 inhibitor IV and were comparable to curcumin. The observed synergistic effect resulting from the reduction of the Aβ1–42 neurotoxicity cascade substantiates the validity of our multifunctional strategy in drug discovery for Alzheimer’s disease. PMID:22781443

Variation in Indole-3-Acetic Acid Production by Wild Saccharomyces cerevisiae and S. paradoxus Strains from Diverse Ecological Sources and Its Effect on Growth.

PubMed

Liu, Yen-Yu; Chen, Hung-Wei; Chou, Jui-Yu

2016-01-01

Phytohormone indole-3-acetic acid (IAA) is the most common naturally occurring and most thoroughly studied plant growth regulator. Microbial synthesis of IAA has long been known. Microbial IAA biosynthesis has been proposed as possibly occurring through multiple pathways, as has been proven in plants. However, the biosynthetic pathways of IAA and the ecological roles of IAA in yeast have not been widely studied. In this study, we investigated the variation in IAA production and its effect on the growth of Saccharomyces cerevisiae and its closest relative Saccharomyces paradoxus yeasts from diverse ecological sources. We found that almost all Saccharomyces yeasts produced IAA when cultured in medium supplemented with the primary precursor of IAA, L-tryptophan (L-Trp). However, when cultured in medium without L-Trp, IAA production was only detected in three strains. Furthermore, exogenous added IAA exerted stimulatory and inhibitory effects on yeast growth. Interestingly, a negative correlation was observed between the amount of IAA production in the yeast cultures and the IAA inhibition ratio of their growth.

Withaferin-A—A Natural Anticancer Agent with Pleitropic Mechanisms of Action

PubMed Central

Lee, In-Chul; Choi, Bu Young

2016-01-01

Cancer, being the second leading cause of mortality, exists as a formidable health challenge. In spite of our enormous efforts, the emerging complexities in the molecular nature of disease progression limit the real success in finding an effective cancer cure. It is now conceivable that cancer is, in fact, a progressive illness, and the morbidity and mortality from cancer can be reduced by interfering with various oncogenic signaling pathways. A wide variety of structurally diverse classes of bioactive phytochemicals have been shown to exert anticancer effects in a large number of preclinical studies. Multiple lines of evidence suggest that withaferin-A can prevent the development of cancers of various histotypes. Accumulating data from different rodent models and cell culture experiments have revealed that withaferin-A suppresses experimentally induced carcinogenesis, largely by virtue of its potent anti-oxidative, anti-inflammatory, anti-proliferative and apoptosis-inducing properties. Moreover, withaferin-A sensitizes resistant cancer cells to existing chemotherapeutic agents. The purpose of this review is to highlight the mechanistic aspects underlying anticancer effects of withaferin-A. PMID:26959007

Withaferin-A--A Natural Anticancer Agent with Pleitropic Mechanisms of Action.

PubMed

Lee, In-Chul; Choi, Bu Young

2016-03-04

Cancer, being the second leading cause of mortality, exists as a formidable health challenge. In spite of our enormous efforts, the emerging complexities in the molecular nature of disease progression limit the real success in finding an effective cancer cure. It is now conceivable that cancer is, in fact, a progressive illness, and the morbidity and mortality from cancer can be reduced by interfering with various oncogenic signaling pathways. A wide variety of structurally diverse classes of bioactive phytochemicals have been shown to exert anticancer effects in a large number of preclinical studies. Multiple lines of evidence suggest that withaferin-A can prevent the development of cancers of various histotypes. Accumulating data from different rodent models and cell culture experiments have revealed that withaferin-A suppresses experimentally induced carcinogenesis, largely by virtue of its potent anti-oxidative, anti-inflammatory, anti-proliferative and apoptosis-inducing properties. Moreover, withaferin-A sensitizes resistant cancer cells to existing chemotherapeutic agents. The purpose of this review is to highlight the mechanistic aspects underlying anticancer effects of withaferin-A.

Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action

PubMed Central

Griffin, Michael O.; Ceballos, Guillermo; Villarreal, Francisco

2010-01-01

Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The firstt of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline’s multiple mechanisms of action as a means to understand their beneficial effects. PMID:20951211

Berberine-induced activation of AMPK increases hepatic FGF21 expression via NUR77.

PubMed

Zhou, Feiye; Bai, Mengyao; Zhang, Yuqing; Zhu, Qin; Zhang, Linlin; Zhang, Qi; Wang, Shushu; Zhu, Kecheng; Liu, Yun; Wang, Xiao; Zhou, Libin

2018-01-08

Fibroblast growth factor 21 (FGF21), a hormone-like protein mainly derived from liver, exhibits multiple beneficial effect on energy metabolism. Similar to FGF21, berberine exerts anti-hyperglycemic and anti-dyslipidemic properties. Previous studies revealed that the beneficial metabolic effect of berberine was attributed to the activation of AMP-activated protein kinase (AMPK). Here we investigated the effect of berberine on FGF21 expression in primary mouse hepatocytes. As expected, berberine induced hepatic FGF21 expression in a dose-dependent and time-dependent manner, along with the increased expression of NUR77, a proved transcription factor of FGF21. Berberine stimulated the phosphorylations of AMPK and acetyl-CoA carboxylase in primary mouse hepatocytes. Adenovirus-mediated overexpression of constitutively active AMPK triggered hepatic FGF21 and NUR77 expressions. The inhibition of AMPK by compound C abolished berberine-stimulated FGF21 and NUR77 expressions. These results suggest that berberine-induced activation of AMPK may contribute to hepatic FGF21 expression via NUR77. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling Local Item Dependence Due to Common Test Format with a Multidimensional Rasch Model

ERIC Educational Resources Information Center

Baghaei, Purya; Aryadoust, Vahid

2015-01-01

Research shows that test method can exert a significant impact on test takers' performance and thereby contaminate test scores. We argue that common test method can exert the same effect as common stimuli and violate the conditional independence assumption of item response theory models because, in general, subsets of items which have a shared…

Baseline Intraocular Pressure Is Associated with Subjective Sensitivity to Physical Exertion in Young Males

ERIC Educational Resources Information Center

Vera, Jesús; Jiménez, Raimundo; García, José Antonio; Perales, José Cesar; Cárdenas, David

2018-01-01

Purpose: The purposes of this study were to (a) investigate the effect of physical effort (cycling for 60 min at 60 ± 5% of individually computed reserve heart-rate capacity), combined with 2 different levels of cognitive demand (2-back, oddball), on intraocular pressure (IOP) and subjective judgments of perceived exertion (ratings of perceived…

THE EFFECTS OF DIFFERENT TRUNK INCLINATIONS ON BILATERAL TRUNK MUSCULAR ACTIVITIES, CENTRE OF PRESSURE AND FORCE EXERTIONS IN STATIC PUSHING POSTURES.

PubMed

Sanjaya, Kadek Heri; Lee, Soomin; Sriwarno, Andar Bagus; Shimomura, Yoshihito; Katsuura, Tetsuo

2014-06-01

In order to reconcile contradictory results from previous studies on manual pushing, a study was conducted to examine the effect of trunk inclination on muscular activities, centre of pressure (COP) and force exertion during static pushing. Ten subjects pushed at 0 degrees, 15 degrees, 30 degrees, and 45 degrees body inclinations in parallel and staggered feet stances. Wall and ground force plates measured pushing force, wall COP, vertical ground reaction force (GRF) and ground COP. Electromyogram data were recorded at 10 trunk muscle sites. Pushing force was found to increase with body inclination. GRF peaked at 15 degrees and reached its lowest level at the 45 degrees inclination. The lowest wall force plate standard deviation of COP displacement was found at the 30 degrees inclination. The lowest low back muscular activity was found at the 15 degrees and 30 degrees inclinations. Based on force exertion, muscular load, and stability, the 30 degrees body inclination was found to be the best posture for static pushing. This study also showed asymmetry in muscular activity and force exertion which has been received less attention in manual pushing studies. These findings will require further study.

Overview and diagnosis of multiple sclerosis.

PubMed

Hunter, Samuel F

2016-06-01

Multiple sclerosis (MS), a chronic inflammatory disease of unknown etiology, involves an immunemediated attack of the central nervous system (CNS) that produces demyelination and axonal/neuronal damage, resulting in characteristic multifocal lesions apparent on magnetic resonance imaging and a variety of neurologic manifestations. The disease pathology is characterized by multifocal lesions within the CNS, in both the white matter and gray matter, with perivenular inflammatory cell infiltrates, demyelination, axonal transection, neuronal degeneration, and gliosis. MS pathogenesis is complex, as it involves both T- and B-cell mechanisms and is heterogeneous in presentation. Relatively recently, the historical 4 core clinical categories of MS were revised in an effort to improve characterization of the clinical course, better identify where a given patient is positioned in the disease spectrum, and to guide clinical studies. In young and middle-aged adults, MS is one of the most common contributors to neurologic disability, and it exerts detrimental effects on a patient's productivity and health-related quality of life. Typically, patients with MS have a long life span, although healthcare utilization increases over time. As a consequence, the disease places a substantial burden on patients and their caregivers/families, as well as employers, the healthcare system, and society.

Gas-Phase Chemistry of Arylimido-Functionalized Hexamolybdates [Mo6O19]2-

NASA Astrophysics Data System (ADS)

Cao, Jie; Wang, QianQian; Liu, Chang; An, ShuQi

2018-04-01

The gas-phase fragmentations of a series of arylimido derivatives of hexamolybdate [Mo6O18(NC6H5-n R n )]2- (2-10, where R = CH3, i-C3H7, OCH3, NO2; n = 1 or 2) versus the parent species [Mo6O19]2- (1) were systematically studied using electrospray tandem mass spectrometry (ESI). Fragmentation of 1 generates two molybdate fragments only, [Mo3O10]2- and [Mo4O13]2-, whereas decomposition of 2-10 went through two dissociation pathways in which path A generates a variety of molybdate fragments via breaking the Mo-N bond followed by the cleavages of the multiple Mo-O bonds, whereas path B produces a range of molybdate fragments with arylimido group via breaking the multiple Mo-O bonds on POM framework. Moreover, the presences of mixed-oxidation-state molybdate fragments are characteristic for the fragmentation. The gas-phase stability order obtained by energy-variable collision-induced dissociation (CID) experiment reveals that 2-10 are generally less stable than 1 and substitution on the benzene ring exerts a considerable effect on the stabilization of the hybrid clusters. [Figure not available: see fulltext.

Ginger-Mechanism of action in chemotherapy-induced nausea and vomiting: A review.

PubMed

Marx, Wolfgang; Ried, Karin; McCarthy, Alexandra L; Vitetta, Luis; Sali, Avni; McKavanagh, Daniel; Isenring, Liz

2017-01-02

Despite advances in antiemetic therapy, chemotherapy-induced nausea and vomiting (CINV) still poses a significant burden to patients undergoing chemotherapy. Nausea, in particular, is still highly prevalent in this population. Ginger has been traditionally used as a folk remedy for gastrointestinal complaints and has been suggested as a viable adjuvant treatment for nausea and vomiting in the cancer context. Substantial research has revealed ginger to possess properties that could exert multiple beneficial effects on chemotherapy patients who experience nausea and vomiting. Bioactive compounds within the rhizome of ginger, particularly the gingerol and shogaol class of compounds, interact with several pathways that are directly implicated in CINV in addition to pathways that could play secondary roles by exacerbating symptoms. These properties include 5-HT 3 , substance P, and acetylcholine receptor antagonism; antiinflammatory properties; and modulation of cellular redox signaling, vasopressin release, gastrointestinal motility, and gastric emptying rate. This review outlines these proposed mechanisms by discussing the results of clinical, in vitro, and animal studies both within the chemotherapy context and in other relevant fields. The evidence presented in this review indicates that ginger possesses multiple properties that could be beneficial in reducing CINV.

Population diversity and multiplicity of infection in Theileria annulata

PubMed Central

Weir, William; Karagenç, Tülin; Gharbi, Mohamed; Simuunza, Martin; Aypak, Suleyman; Aysul, Nuran; Darghouth, Mohamed Aziz; Shiels, Brian; Tait, Andrew

2011-01-01

The tick-borne apicomplexan parasite Theileria annulata is endemic in many sub-tropical countries and causes the bovine disease tropical theileriosis. Although the parasite is known to be highly diverse, detailed information is lacking on the genetic structure of natural populations and levels of multiplicity of infection in the cattle host. With the widespread deployment of live attenuated vaccines and the emergence of drug-resistant parasites in the field, it is vital to appreciate the factors which shape genetic diversity of the parasite both within individual hosts and in the wider population. This study addresses these issues and represents an extensive genetic analysis of T. annulata populations in two endemic countries utilising a high-throughput adaptation of a micro- and mini-satellite genotyping system. Parasite material was collected from infected cattle in defined regions of Turkey and Tunisia to allow a variety of analyses to be conducted. All animals (n = 305) were found to harbour multiple parasite genotypes and only two isolates shared an identical predominant multi-locus profile. A modelling approach was used to demonstrate that host age, location and vaccination status play a measurable role in determining multiplicity of infection in an individual animal. Age was shown to positively correlate with multiplicity of infection and while positive vaccination status exerted a similar effect, it was shown to be due not simply to the presence of the immunising genotype. Importantly, no direct evidence was found for the immunising genotype spreading or recombining within the local parasite community. Genetic analysis confirmed the tentative conclusion of a previous study that the parasite population appears to be, in general, panmictic. Nevertheless, evidence supporting linkage disequilibrium and a departure from panmixia was uncovered in some localities and a number of explanations for these findings are advanced. PMID:20833170

Implicit theories about willpower predict the activation of a rest goal following self-control exertion.

PubMed

Job, Veronika; Bernecker, Katharina; Miketta, Stefanie; Friese, Malte

2015-10-01

Past research indicates that peoples' implicit theories about the nature of willpower moderate the ego-depletion effect. Only people who believe or were led to believe that willpower is a limited resource (limited-resource theory) showed lower self-control performance after an initial demanding task. As of yet, the underlying processes explaining this moderating effect by theories about willpower remain unknown. Here, we propose that the exertion of self-control activates the goal to preserve and replenish mental resources (rest goal) in people with a limited-resource theory. Five studies tested this hypothesis. In Study 1, individual differences in implicit theories about willpower predicted increased accessibility of a rest goal after self-control exertion. Furthermore, measured (Study 2) and manipulated (Study 3) willpower theories predicted an increased preference for rest-conducive objects. Finally, Studies 4 and 5 provide evidence that theories about willpower predict actual resting behavior: In Study 4, participants who held a limited-resource theory took a longer break following self-control exertion than participants with a nonlimited-resource theory. Longer resting time predicted decreased rest goal accessibility afterward. In Study 5, participants with an induced limited-resource theory sat longer on chairs in an ostensible product-testing task when they had engaged in a task requiring self-control beforehand. This research provides consistent support for a motivational shift toward rest after self-control exertion in people holding a limited-resource theory about willpower. (c) 2015 APA, all rights reserved).

Development of an assay to assess genotoxicity by particulate matter extract

PubMed Central

Priftis, Alexandros; Papikinos, Konstantinos; Koukoulanaki, Marina; Kerasioti, Efthalia; Stagos, Dimitrios; Konstantinopoulos, Konstantinos; Spandidos, Demetrios A.; Kermenidou, Marianthi; Karakitsios, Spyros; Sarigiannis, Dimosthenis; Tsatsakis, Aristides M.; Kouretas, Demetrios

2017-01-01

The current study describes a method for assessing the oxidative potential of common environmental stressors (ambient air particulate matter), using a plasmid relaxation assay where the extract caused single-strand breaks, easily visualised through electrophoresis. This assay utilises a miniscule amount (11 µg) of particulate matter (PM) extract compared to other, cell-based methods (~3,000 µg). The negative impact of air pollution on human health has been extensively recognised. Among the air pollutants, PM plays an eminent role, as reflected in the broad scientific interest. PM toxicity highly depends on its composition (metals and organic compounds), which in turn has been linked to multiple health effects (such as cardiorespiratory diseases and cancer) through multiple toxicity mechanisms; the induction of oxidative stress is considered a major mechanism among these. In this study, the PM levels, oxidative potential, cytotoxicity and genotoxicity of PM in the region of Larissa, Greece were examined using the plasmid relaxation assay. Finally, coffee extracts from different varieties, derived from both green and roasted seeds, were examined for their ability to inhibit PM-induced DNA damage. These extracts also exerted an inhibitory effect on xanthine oxidase and catalase, but had no effect against superoxide dismutase. Overall, this study highlights the importance of assays for assessing the oxidative potential of widespread environmental stressors (PM), as well as the antioxidant capacity of beverages and food items, with the highlight being the development of a plasmid relaxation assay to assess the genotoxicity caused by PM using only a miniscule amount. PMID:28260086

Interactions between child and parent temperament and child behavior problems.

PubMed

Rettew, David C; Stanger, Catherine; McKee, Laura; Doyle, Alicia; Hudziak, James J

2006-01-01

Few studies of temperament have tested goodness-of-fit theories of child behavior problems. In this study, we test the hypothesis that interactions between child and parent temperament dimensions predict levels of child psychopathology after controlling for the effects of these dimensions individually. Temperament and psychopathology were assessed in a total of 175 children (97 boys, 78 girls; mean age, 10.99 years; SD, 3.66 years) using composite scores from multiple informants of the Junior Temperament and Character Inventory and the Achenbach System of Empirically Based Assessment. Parent temperament was assessed using the adult version of the Temperament and Character Inventory. Statistical analyses included multiple regression procedures to assess the contribution of child-parent temperament interactions after controlling for demographic variables, other types of child psychopathology, and the individual Temperament and Character Inventory and Junior Temperament and Character Inventory dimensions. Interactions between child and parent temperament dimensions predicted higher levels of externalizing, internalizing, and attention problems over and above the effects of these dimensions alone. Among others, the combination of high child novelty seeking with high maternal novelty was associated with child attention problems, whereas the combination of high child harm avoidance and high father harm avoidance was associated with increased child internalizing problems. Many child temperament dimensions also exerted significant effects independently. The association between a child temperament trait and psychopathology can be dependent upon the temperament of parents. These data lend support to previous theories of the importance of goodness-of-fit.

Non-coding RNAs and Berberine: A new mechanism of its anti-diabetic activities.

PubMed

Chang, Wenguang

2017-01-15

Type 2 Diabetes (T2D) is a metabolic disease with high mortality and morbidity. Non-coding RNAs, including small and long non-coding RNAs, are a novel class of functional RNA molecules that regulate multiple biological functions through diverse mechanisms. Studies in the last decade have demonstrated that non-coding RNAs may represent compelling therapeutic targets and play important roles in regulating the course of insulin resistance and T2D. Berberine, a plant-based alkaloid, has shown promise as an anti-hyperglycaemic, anti-hyperlipidaemic agent against T2D. Previous studies have primarily focused on a diverse array of efficacy end points of berberine in the pathogenesis of metabolic syndromes and inflammation or oxidative stress. Currently, an increasing number of studies have revealed the importance of non-coding RNAs as regulators of the anti-diabetic effects of berberine. The regulation of non-coding RNAs has been associated with several therapeutic actions of berberine in T2D progression. Thus, this review summarizes the anti-diabetic mechanisms of berberine by focusing on its role in regulating non-coding RNA, thus demonstrating that berberine exerts global anti-diabetic effects by targeting non-coding RNAs and that these effects involve several miRNAs, lncRNAs and multiple signal pathways, which may enhance the current understanding of the anti-diabetic mechanism actions of berberine and provide new pathological targets for the development of berberine-related drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of work-family-school role conflicts and role-related social support on burnout in Registered Nurses: a structural equation modelling approach.

PubMed

Goong, Hwasoo; Xu, Lijuan; Li, Chun-Yu

2016-11-01

To examine the effects of work-family-school role conflicts and role-related social support (RRSS) on burnout of nurses pursuing an advanced degree. A predictive correlational cross-sectional study design was used. Nurses were found to be a high-risk group for burnout, even more so among nurses pursuing an advanced degree. When nurses with a professional career marry and decide to become students, inter-role conflicts and burnout are possible outcomes of the resulting multiple roles. Using convenience sampling, data were collected from October 2011-May 2012. A questionnaire about work-family-school role conflicts, RRSS, burnout and general information was completed by 286 nurses pursuing an advanced degree at 12 hospitals in Korea. Data were analysed using SPSS and structural equation modelling with the Analysis of Moment Structures program. The proposed model provided a good fit to the obtained data. Work-family-school role conflicts and social support exerted significant effects on burnout. Role-related social support was found to play a partial mediating role between work-family-school role conflicts and burnout. The findings of this study imply that RRSS significantly directly and indirectly influences burnout among the nurses pursuing an advanced degree. It is necessary for nursing managers to consider implementing family- and school-friendly policies (e.g. flexible work schedules) to help nurses to manage their multiple roles and thereby decrease their burnout rate. © 2016 John Wiley & Sons Ltd.

Minocycline: far beyond an antibiotic

PubMed Central

Garrido-Mesa, N; Zarzuelo, A; Gálvez, J

2013-01-01

Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein. PMID:23441623

Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants

PubMed Central

Willis, Daniel N.; Liu, Boyi; Ha, Michael A.; Jordt, Sven-Eric; Morris, John B.

2011-01-01

Menthol, the cooling agent in peppermint, is added to almost all commercially available cigarettes. Menthol stimulates olfactory sensations, and interacts with transient receptor potential melastatin 8 (TRPM8) ion channels in cold-sensitive sensory neurons, and transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing channel. It is highly controversial whether menthol in cigarette smoke exerts pharmacological actions affecting smoking behavior. Using plethysmography, we investigated the effects of menthol on the respiratory sensory irritation response in mice elicited by smoke irritants (acrolein, acetic acid, and cyclohexanone). Menthol, at a concentration (16 ppm) lower than in smoke of mentholated cigarettes, immediately abolished the irritation response to acrolein, an agonist of TRPA1, as did eucalyptol (460 ppm), another TRPM8 agonist. Menthol's effects were reversed by a TRPM8 antagonist, AMTB. Menthol's effects were not specific to acrolein, as menthol also attenuated irritation responses to acetic acid, and cyclohexanone, an agonist of the capsaicin receptor, TRPV1. Menthol was efficiently absorbed in the respiratory tract, reaching local concentrations sufficient for activation of sensory TRP channels. These experiments demonstrate that menthol and eucalyptol, through activation of TRPM8, act as potent counterirritants against a broad spectrum of smoke constituents. Through suppression of respiratory irritation, menthol may facilitate smoke inhalation and promote nicotine addiction and smoking-related morbidities.— Willis, D. N., Liu, B., Ha, M. A., Jordt, S.-E., Morris, J. B. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. PMID:21903934

Biphasic effects of FGF2 on odontoblast differentiation involve changes in the BMP and Wnt signaling pathways.

PubMed

Sagomonyants, Karen; Mina, Mina

2014-08-01

Odontoblast differentiation during physiological and reparative dentinogenesis is dependent upon multiple signaling molecules, including fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs) and Wingless/Integrated (Wnt) ligands. Recent studies in our laboratory showed that continuous exposure of primary dental pulp cultures to FGF2 exerted biphasic effects on the expression of markers of dentinogenesis. In the present study, we examined the possible involvement of the BMP and Wnt signaling pathways in mediating the effects of FGF2 on dental pulp cells. Our results showed that stimulatory effects of FGF2 on dentinogenesis during the proliferation phase of growth were associated with increased expression of the components of the BMP (Bmp2, Dlx5, Msx2, Osx) and Wnt (Wnt10a, Wisp2) pathways, and decreased expression of an inhibitor of the Wnt signaling, Nkd2. Further addition of FGF2 during the differentiation/mineralization phase of growth resulted in decreased expression of components of the BMP signaling (Bmp2, Runx2, Osx) and increased expression of inhibitors of the Wnt signaling (Nkd2, Dkk3). This suggests that both BMP and Wnt pathways may be involved in mediating the effects of FGF2 on dental pulp cells.

Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

PubMed

Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

2018-02-05

Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

Egg and Soy-Derived Peptides and Hydrolysates: A Review of Their Physiological Actions against Diabetes and Obesity.

PubMed

C de Campos Zani, Stepheny; Wu, Jianping; B Chan, Catherine

2018-04-28

Type 2 diabetes and obesity are two chronic conditions associated with the metabolic syndrome and their prevalences are increasing worldwide. The investigation of food protein-derived bioactive peptides that can improve the pathophysiology of diabetes or obesity while causing minimal side effects is desired. Egg and soy proteins generate bioactive peptides with multiple biological effects, exerting nutritional and physiological benefits. This review focuses on the anti-diabetic and anti-obesity effects of egg- and soy-derived peptides and hydrolysates in vivo and in vitro relevant to these conditions. Studies using the intact protein were considered only when comparing the results with the hydrolysate or peptides. In vivo evidence suggests that bioactive peptides from egg and soy can potentially be used to manage elements of glucose homeostasis in metabolic syndrome; however, the mechanisms of action on glucose and insulin metabolism, and the interaction between peptides and their molecular targets remain unclear. Optimizing the production of egg- and soy-derived peptides and standardizing the physiological models to study their effects on diabetes and obesity could help to clarify the effects of these bioactive peptides in metabolic syndrome-related conditions.

Neuropsychiatric Effects of Antimicrobial Agents.

PubMed

Zareifopoulos, Nicholas; Panayiotakopoulos, George

2017-05-01

Antimicrobial drugs used in clinical practice are selected on the basis of their selective toxicity against bacterial cells. However, all exhibit multiple offsite interactions with eukaryotic cell structures, resulting in adverse reactions during antimicrobial pharmacotherapy. A multitude of these side effects involve the nervous system as antimicrobials at clinically relevant concentrations seem to interact with many of the same molecules usually implicated in the action of psychotropic drugs. The importance of such events cannot be overstated, as the misdiagnosis of an adverse drug reaction as a symptom of a primary psychiatric or neurological disorder entails great suffering for the patient affected as well as significant costs for the healthcare system. The neuropsychiatric effects of antimicrobial drugs are extensively documented in the literature. A number of antimicrobial drugs have the potential to exert CNS effects and many are associated with stimulant, psychotomimetic and epileptogenic properties, mediated by GABA antagonism (beta-lactams, quinolones and clarithromycin), NMDA agonism (D-cycloserine, aminoglycosides, and perhaps quinolones), MAO inhibition (linezolid, metronidazole and isoniazid weakly) as well as more exotic mechanisms, as in the case of trimethoprim, isoniazid, ethambutol, rifampicin and the tetracyclines. While those effects are generally undesirable, they may also under certain circumstances be beneficial, and further research is warranted in that direction.

An exogenous hydrogen sulphide donor, NaHS, inhibits the apoptosis signaling pathway to exert cardio-protective effects in a rat hemorrhagic shock model.

PubMed

Xu, Yanjie; Dai, Xiongwei; Zhu, Danxia; Xu, Xiaoli; Gao, Cao; Wu, Changping

2015-01-01

Hydrogen sulfide (H2S) has been reported to be interwined in multiple systems, specifically in the cardiovascular system. However, the mechanisms underlying remain controversial. In the present study, we assessed the cardio-protective effects of H2S in the rat hemorrhagic shock model. Hemorrhagic shock was induced in adult male Sprague-Dawley rats by drawing blood from the femoral artery to maintain the mean arterial pressure at 35-40 mmHg for 1.5 h. The rats were assigned to four groups and the H2S donor, NaHS (28 μmol/kg, i.p.), was injected before the resuscitation in certain groups. After resuscitation the animals were observed and then killed to harvest the hearts. The morphological investigation and ultrastructural analyses were done and apoptotic cells were detected. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. Resuscitated hemorrhagic shock induced heart injury and significantly increased the levels of serum myocardial enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, it caused marked increase of apoptotic cells in heart tissue. Moreover, the expression of death receptor Fas and Fas-ligand, as well as the expression of apoptosis-relevant proteins active-caspase 3 and active-caspase 8 were markedly increased. Administration of NaHS significantly ameliorated hemorrhagic shock caused hemodynamic deterioration, decreased myocardial enzymes elevation, protected myocardial ultrastructure, and inhibited the expression of apoptosis-relevant proteins. It suggested that H2S might exert its cardio-protective roles via both the extrinsic Fas/FasL/caspase-8/caspase-3 pathway and the intrinsic mitochondria-involved pathways.

ENHANCED 5-HT1A RECEPTOR-DEPENDENT FEEDBACK CONTROL OVER DORSAL RAPHE SEROTONIN NEURONS IN THE SERT KNOCKOUT MOUSE

PubMed Central

Soiza-Reilly, Mariano; Goodfellow, Nathalie M.; Lambe, Evelyn K.; Commons, Kathryn G.

2014-01-01

5-HT1A receptors are widely expressed in the brain and play a critical role in feedback inhibition of serotonin (5-HT) neurons through multiple mechanisms. Yet, it remains poorly understood how these feedback mechanisms, particularly those involving long-range projections, adapt in mood disorders. Here, we examined several aspects of 5-HT1A receptor function in the 5-HT transporter knockout mouse (SERT-KO), a model of vulnerability to stress and mood disorders. We found that in comparison to wild-type (WT) mice, SERT-KO mice had more passive coping in response to acute swim stress and this was accompanied by hypo-activation of medial prefrontal cortex (mPFC) Fos expression. Both of these effects were reversed by systemically blocking 5-HT1A receptors. Ex-vivo electrophysiological experiments showed that 5-HT exerted greater 5-HT1A-mediated inhibitory effects in the mPFC of SERT-KO mice compared to WT. Since 5-HT1A receptors in the mPFC provide a key feedback regulation of the dorsal raphe nucleus (DRN), we used a disinhibition strategy to examined endogenous feedback control of 5-HT neurons. Blocking 5-HT1A receptors disinhibited several fold more 5-HT neurons in the DRN of SERT-KO than in WT mice, revealing the presence of enhanced feedback inhibition of 5-HT neurons in the SERT-KO. Taken together our results indicate that increased stress sensitivity in the SERT-KO is associated with the enhanced capacity of 5-HT1A receptors to inhibit neurons in the mPFC as well as to exert feedback inhibition of DRN 5-HT neurons. PMID:25261781

Electrodynamic multiple-scattering method for the simulation of optical trapping atop periodic metamaterials

NASA Astrophysics Data System (ADS)

Yannopapas, Vassilios; Paspalakis, Emmanuel

2018-07-01

We present a new theoretical tool for simulating optical trapping of nanoparticles in the presence of an arbitrary metamaterial design. The method is based on rigorously solving Maxwell's equations for the metamaterial via a hybrid discrete-dipole approximation/multiple-scattering technique and direct calculation of the optical force exerted on the nanoparticle by means of the Maxwell stress tensor. We apply the method to the case of a spherical polystyrene probe trapped within the optical landscape created by illuminating of a plasmonic metamaterial consisting of periodically arranged tapered metallic nanopyramids. The developed technique is ideally suited for general optomechanical calculations involving metamaterial designs and can compete with purely numerical methods such as finite-difference or finite-element schemes.

Effects of the Visual Exercise Environments on Cognitive Directed Attention, Energy Expenditure and Perceived Exertion

PubMed Central

Rogerson, Mike; Barton, Jo

2015-01-01

Green exercise research often reports psychological health outcomes without rigorously controlling exercise. This study examines effects of visual exercise environments on directed attention, perceived exertion and time to exhaustion, whilst measuring and controlling the exercise component. Participants completed three experimental conditions in a randomized counterbalanced order. Conditions varied by video content viewed (nature; built; control) during two consistently-ordered exercise bouts (Exercise 1: 60% VO2peakInt for 15-mins; Exercise 2: 85% VO2peakInt to voluntary exhaustion). In each condition, participants completed modified Backwards Digit Span tests (a measure of directed attention) pre- and post-Exercise 1. Energy expenditure, respiratory exchange ratio and perceived exertion were measured during both exercise bouts. Time to exhaustion in Exercise 2 was also recorded. There was a significant time by condition interaction for Backwards Digit Span scores (F2,22 = 6.267, p = 0.007). Scores significantly improved in the nature condition (p < 0.001) but did not in the built or control conditions. There were no significant differences between conditions for either perceived exertion or physiological measures during either Exercise 1 or Exercise 2, or for time to exhaustion in Exercise 2. This was the first study to demonstrate effects of controlled exercise conducted in different visual environments on post-exercise directed attention. Via psychological mechanisms alone, visual nature facilitates attention restoration during moderate-intensity exercise. PMID:26133125

Effects of the Visual Exercise Environments on Cognitive Directed Attention, Energy Expenditure and Perceived Exertion.

PubMed

Rogerson, Mike; Barton, Jo

2015-06-30

Green exercise research often reports psychological health outcomes without rigorously controlling exercise. This study examines effects of visual exercise environments on directed attention, perceived exertion and time to exhaustion, whilst measuring and controlling the exercise component. Participants completed three experimental conditions in a randomized counterbalanced order. Conditions varied by video content viewed (nature; built; control) during two consistently-ordered exercise bouts (Exercise 1: 60% VO2peakInt for 15-mins; Exercise 2: 85% VO2peakInt to voluntary exhaustion). In each condition, participants completed modified Backwards Digit Span tests (a measure of directed attention) pre- and post-Exercise 1. Energy expenditure, respiratory exchange ratio and perceived exertion were measured during both exercise bouts. Time to exhaustion in Exercise 2 was also recorded. There was a significant time by condition interaction for Backwards Digit Span scores (F2,22 = 6.267, p = 0.007). Scores significantly improved in the nature condition (p < 0.001) but did not in the built or control conditions. There were no significant differences between conditions for either perceived exertion or physiological measures during either Exercise 1 or Exercise 2, or for time to exhaustion in Exercise 2. This was the first study to demonstrate effects of controlled exercise conducted in different visual environments on post-exercise directed attention. Via psychological mechanisms alone, visual nature facilitates attention restoration during moderate-intensity exercise.

The Role of Motivation, Glucose and Self-Control in the Antisaccade Task

PubMed Central

Kelly, Claire L.; Sünram-Lea, Sandra I.; Crawford, Trevor J.

2015-01-01

Research shows that self-control is resource limited and there is a gradual weakening in consecutive self-control task performance akin to muscle fatigue. A body of evidence suggests that the resource is glucose and consuming glucose reduces this effect. This study examined the effect of glucose on performance in the antisaccade task - which requires self-control through generating a voluntary eye movement away from a target - following self-control exertion in the Stroop task. The effects of motivation and individual differences in self-control were also explored. In a double-blind design, 67 young healthy adults received a 25g glucose or inert placebo drink. Glucose did not enhance antisaccade performance following self-control exertion in the Stroop task. Motivation however, predicted performance on the antisaccade task; more specifically high motivation ameliorated performance decrements observed after initial self-control exertion. In addition, individuals with high levels of self-control performed better on certain aspects of the antisaccade task after administration of a glucose drink. The results of this study suggest that the antisaccade task might be a powerful paradigm, which could be used as a more objective measure of self-control. Moreover, the results indicate that level of motivation and individual differences in self-control should be taken into account when investigating deficiencies in self-control following prior exertion. PMID:25826334

Semipurified Ethyl Acetate Partition of Methanolic Extract of Melastoma malabathricum Leaves Exerts Gastroprotective Activity Partly via Its Antioxidant-Antisecretory-Anti-Inflammatory Action and Synergistic Action of Several Flavonoid-Based Compounds

PubMed Central

Ismail Suhaimy, Noor Wahida; Noor Azmi, Ahmad Khusairi; Mohtarrudin, Norhafizah; Cheema, Manraj Singh

2017-01-01

Recent study has demonstrated the gastroprotective activity of crude methanolic extract of M. malabathricum leaves. The present study evaluated the gastroprotective potential of semipurified extracts (partitions): petroleum ether, ethyl acetate (EAMM), and aqueous obtained from the methanolic extract followed by the elucidation of the gastroprotective mechanisms of the most effective partition. Using the ethanol-induced gastric ulcer assay, all partitions exerted significant gastroprotection, with EAMM being the most effective partition. EAMM significantly (i) reduced the volume and acidity (free and total) while increasing the pH of gastric juice and enhanced the gastric wall mucus secretion when assessed using the pylorus ligation assay, (ii) increased the enzymatic and nonenzymatic antioxidant activity of the stomach tissue, (iii) lost its gastroprotective activity following pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME; NO blocker) or carbenoxolone (CBXN; NP-SH blocker), (iv) exerted antioxidant activity against various in vitro oxidation assays, and (v) showed moderate in vitro anti-inflammatory activity via the LOX-modulated pathway. In conclusion, EAMM exerts a remarkable NO/NP-SH-dependent gastroprotective effect that is attributed to its antisecretory and antioxidant activities, ability to stimulate the gastric mucus production and endogenous antioxidant system, and synergistic action of several gastroprotective-induced flavonoids. PMID:28168011

Ergonomics and patient handling.

PubMed

McCoskey, Kelsey L

2007-11-01

This study aimed to describe patient-handling demands in inpatient units during a 24-hour period at a military health care facility. A 1-day total population survey described the diverse nature and impact of patient-handling tasks relative to a variety of nursing care units, patient characteristics, and transfer equipment. Productivity baselines were established based on patient dependency, physical exertion, type of transfer, and time spent performing the transfer. Descriptions of the physiological effect of transfers on staff based on patient, transfer, and staff characteristics were developed. Nursing staff response to surveys demonstrated how patient-handling demands are impacted by the staff's physical exertion and level of patient dependency. The findings of this study describe the types of transfers occurring in these inpatient units and the physical exertion and time requirements for these transfers. This description may guide selection of the most appropriate and cost-effective patient-handling equipment required for specific units and patients.

Influence of Protein-Phenolic Complex on the Antioxidant Capacity of Flaxseed (Linum usitatissimum L.) Products.

PubMed

Guimarães Drummond E Silva, Fernanda; Miralles, Beatriz; Hernández-Ledesma, Blanca; Amigo, Lourdes; Iglesias, Amadeu Hoshi; Reyes Reyes, Felix Guillermo; Netto, Flavia Maria

2017-02-01

The impact of the naturally present phenolic compounds and/or proteins on the antioxidant capacity of flaxseed products (phenolic fraction, protein concentrates, and hydrolysates) before and after simulated gastrointestinal digestion was studied. For that, whole and phenolic reduced products were assessed. Four glycosylated phenolic compounds (secoisolariciresinol and ferulic, p-coumaric, and caffeic acids) were identified in flaxseed products. Phenolic fraction exerts the highest antioxidant capacity that increased by alkaline hydrolysis and by simulated gastrointestinal digestion. The action of Alcalase and digestive enzymes resulted in an increase of the antioxidant capacity of whole and phenolic reduced products. Principal component analysis showed that proteinaceous samples act as antioxidant is by H + transfer, while those samples containing phenolic compounds exert their effects by both electron donation and H + transfer mechanisms. Protein/peptide-phenolic complexation, confirmed by fluorescence spectra, exerted a positive effect on the antioxidant capacity, mainly in protein concentrates.

Overexpression of GDNF in the uninjured DRG exerts analgesic effects on neuropathic pain following segmental spinal nerve ligation in mice.

PubMed

Takasu, Kumiko; Sakai, Atsushi; Hanawa, Hideki; Shimada, Takashi; Suzuki, Hidenori

2011-11-01

Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein (EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia in association with an increase in GDNF protein expression in each virus injection site, whereas injection into the injured L5 DRG or plantar skin had no effects. These results suggest that GDNF exerts its analgesic effects in the neuropathic pain state by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by the uninjured DRG neurons. This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by these neurons. Therefore, research focusing on these GDNF-dependent neurons in the uninjured DRG would provide a new strategy for treating neuropathic pain. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Vertebral hemangiomas in the thoracic spine of multiple sclerosis patients are connected with fewer demyelinating lesions at the same level. Possible impact on pathophysiology and clinical course.

PubMed

Anagnostouli, Maria; Katsavos, Serafeim; Kyrozis, Andreas; Gontika, Maria; Voumvourakis, Konstantinos I; Kapaki, Elisabeth

2016-08-01

Mechanisms of angiogenesis regulate multiple sclerosis (MS) lesions' evolution, displaying both neuroprotective and harmful effects. Factors traditionally considered as purely angiogenic, like vascular endothelial growth factor (VEGF), exert complex heterogenous actions on both neural and vascular malformation-derived tissues. Aim of this retrospective study was to examine, for the first time, potential associations between the presence of common vascular malformations, like vertebral hemangiomas (VHs), and several clinico-radiological MS parameters. 236 MS patients who were followed in our Outpatient Clinic were recruited in this study. Outcome measures concerned demographics, disease-derived variables, and MS-lesions' distribution in VHs - positive and negative patients. All data were collected retrospectively. Potential correlations were assessed with univariate statistical analyses (p = 0.05), followed by multivariate regression models, for purposes of confounder-effects elimination. VH presence showed significant negative correlations with presence of MS lesions in the thoracic (p = 0.005 for thoracic VHs), but not the cervical cord. Trends towards negative associations of VH presence with subtentorial MS lesions and positive family history for MS were also observed. Our observations suggest that VH presence may reduce the risk of thoracic demyelinating lesions in MS patients. They could be explained as part of a multifaceted angiogenic process, concomitantly enhancing neural repair and abnormal hemangioma vascularization.

Sequential effects in pigeon delayed matching-to-sample performance.

PubMed

Roitblat, H L; Scopatz, R A

1983-04-01

Pigeons were tested in a three-alternative delayed matching-to-sample task in which second-choices were permitted following first-choice errors. Sequences of responses both within and between trials were examined in three experiments. The first experiment demonstrates that the sample information contained in first-choice errors is not sufficient to account for the observed pattern of second choices. This result implies that second-choices following first-choice errors are based on a second examination of the contents of working memory. Proactive interference was found in the second experiment in the form of a dependency, beyond that expected on the basis of trial independent response bias, of first-choices from one trial on the first-choice emitted on the previous trial. Samples from the previous trial were not found to exert a significant influence on later trials. The magnitude of the intertrial association (Experiment 3) did not depend on the duration of the intertrial interval. In contrast, longer intertrial intervals and longer sample durations did facilitate choice accuracy, by strengthening the association between current samples and choices. These results are incompatible with a trace-decay and competition model; they suggest strongly that multiple influences act simultaneously and independently to control delayed matching-to-sample responding. These multiple influences include memory for the choice occurring on the previous trial, memory for the sample, and general effects of trial spacing.

Interferon-β Modulates Inflammatory Response in Cerebral Ischemia.

PubMed

Kuo, Ping-Chang; Scofield, Barbara A; Yu, I-Chen; Chang, Fen-Lei; Ganea, Doina; Yen, Jui-Hung

2016-01-08

Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Comprehensive and Holistic Analysis of HT-29 Colorectal Cancer Cells and Tumor-Bearing Nude Mouse Model: Interactions Among Fractions Derived From the Chinese Medicine Formula Tian Xian Liquid in Effects on Human Colorectal Carcinoma.

PubMed

Leigh, Annballaw Bridget; Cheung, Ho Pan; Lin, Li-Zhu; Ng, Tzi Bun; Lao, Lixing; Zhang, Yanbo; Zhang, Zhang-Jin; Tong, Yao; Sze, Stephen Cho Wing

2017-09-01

The Chinese medicine formula Tian Xian Liquid (TXL) has been used clinically for cancer therapy in China for more than 25 years. However, the comprehensive and holistic effects of its bioactive fractions for various antitumor therapeutic effects have not been unraveled. This is the first study to scientifically elucidate the holistic effect of Chinese medicine formula for treating colon cancer, hence allowing a better understanding of the essence of Chinese medicine formula, through the comparison of the actions of TXL and its functional constituent fractions, including ethyl acetate (EA), butanol (BU), and aqueous (WA) fractions. Tissue-specific proliferative/antiproliferative effects of these fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using the MTT assay. Their modulations on the expression of markers of antiproliferation, antimetastasis, reversion of multidrug resistance in treated HT-29 cells were examined with real-time polymerase chain reaction and Western blot analysis, and their modulations in a xenografted nude mouse model were examined by Western blot analysis. Results revealed that EA fraction slightly inhibited the proliferation of HT-29 cells, but tissue-specifically exerted the most potent antiproliferative effect on splenocytes. On the contrary, only TXL and BU fraction tissue-specifically contributed to the proliferation of splenocytes, but inhibited the proliferation of HT-29 cells. WA fraction exerted the most potent antiproliferative effect on HT-29 cells and also the strongest inhibitory action on tumor size in the nude mouse model in our previous study. In the HT-29 model, TXL and WA fraction exerted the most pronounced effect on upregulation of p21 mRNA and protein; TXL, and EA and WA fractions exerted the effect on downregulation of G1 phase cell cycle protein, cyclin D1 mRNA and protein; EA and BU fractions exerted the most prominent anti-invasive effect on anti-invasion via downregulation of MMP-1 mRNA; TXL potently reversed most multidrug resistance via downregulation of MDR-1 protein. In conclusion, the comprehensive and holistic effects of TXL were demonstrated with ( a) mutual accentuation and mutual enhancement, ( b) mutual counteraction and mutual suppression, and ( c) mutual antagonism among the 3 constituent fractions. Moreover, the design of the present study may lead to further development of more tissue-specific effective drugs with minimal side effects for clinical use in combating carcinoma.

The effects of vinblastine on endothelial cells.

PubMed

Gallagher, H; Carroll, W M; Dowd, M; Rochev, Y

2008-01-01

The development of drug-eluting stents to combat the problem of in-stent restenosis has revolutionized interventional cardiology. However, concerns have emerged about the risk of late angiographic stent thromboses associated with drug-eluting stents. It has been shown that noncytotoxic concentrations of paclitaxel exert an antiangiogenic effect, suggesting that paclitaxel and similar agents may inhibit key cellular functions in a threshold-independent manner. In this study, the effect of vinblastine, an antimitotic drug, on endothelial cells is analyzed. It is investigated whether noncytotoxic concentrations of the drug could exert an antirestenotic effect. The change in levels of cell proliferation, activity, and viability in human umbilical vein endothelial cells was measured at a range of concentrations and over a number of time points. Also, the level of apoptotic activity in response to vinblastine was analyzed. This study shows that the concentration of vinblastine most appropriate in restenosis treatment would be between 0.1 and 1 nM. At this concentration, vinblastine exerts a distinct biological effect without causing an increase in apoptotic activity. These results emphasize the importance of finding an appropriate concentration window in order to minimize the risk of delayed endothelialization and thrombosis.

Effects of retinoic acids on the dendritic morphology of cultured hippocampal neurons.

PubMed

Liu, Ying; Kagechika, Hiroyuki; Ishikawa, Junko; Hirano, Hitoshi; Matsukuma, Satoshi; Tanaka, Kazuko; Nakamura, Shoji

2008-08-01

Vitamin A-derived retinoic acids (RAs) are known to exert a variety of biological actions, including modulatory effects on cell differentiation and apoptosis. A recent study has demonstrated that 13-cis-RA and all-trans-RA suppressed neurogenesis in the dentate gyrus of the hippocampus in adult mice. The present experiments were performed to see whether 13-cis-RA and all-trans-RA could alter the dendritic morphology of cultured hippocampal neurons via RA receptors: retinoic acid receptor (RAR) and retinoid X receptor (RXR). High doses of 13-cis-RA and all-trans-RA exerted a negative effect on the cultured hippocampal neurons, while a low dose of 13-cis-RA but not all-trans-RA caused a positive effect. The negative changes induced by 13-cis-RA and all-trans-RA were antagonized by RXR antagonists and RAR antagonists, respectively. The positive changes induced by a low dose of 13-cis-RA were blocked by both RXR antagonists and RAR antagonists. These results suggest that RAs at high concentrations cause a negative effect on the dendritic morphology of cultured hippocampal neurons through RA receptors, while RAs at low concentrations exert a positive influence on cultured hippocampal neurons.

Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats.

PubMed

An, Yan; Chen, Chong; Inoue, Takeshi; Nakagawa, Shin; Kitaichi, Yuji; Wang, Ce; Izumi, Takeshi; Kusumi, Ichiro

2016-10-03

The functional role of serotonergic projections from the median raphe nucleus (MRN) to the dorsal hippocampus (DH) in anxiety remains understood poorly. The purpose of the present research was to examine the functional role of this pathway, using the contextual fear conditioning (CFC) model of anxiety. We show that intra-MRN microinjection of mirtazapine, a noradrenergic and specific serotonergic antidepressant, reduced freezing in CFC without affecting general motor activity dose-dependently, suggesting an anxiolytic-like effect. In addition, intra-MRN microinjection of mirtazapine dose-dependently increased extracellular concentrations of serotonin (5-HT) but not dopamine in the DH. Importantly, intra-DH pre-microinjection of WAY-100635, a 5-HT1A antagonist, significantly attenuated the effect of mirtazapine on freezing. These results, for the first time, suggest that activation of the MRN-DH 5-HT1A pathway exerts an anxiolytic-like effect in CFC. This is consistent with the literature that the hippocampus is essential for retrieval of contextual memory and that 5-HT1A receptor activation in the hippocampus primarily exerts an inhibitory effect on the neuronal activity. Copyright © 2016 Elsevier Inc. All rights reserved.

ASP6537, a novel highly selective cyclooxygenase-1 inhibitor, exerts potent antithrombotic effect without "aspirin dilemma".

PubMed

Sakata, Chinatsu; Kawasaki, Tomihisa; Kato, Yasuko; Abe, Masaki; Suzuki, Ken-ichi; Ohmiya, Makoto; Funatsu, Toshiyuki; Morita, Yoshiaki; Okada, Masamichi

2013-07-01

Aspirin inhibits both the cyclooxygenase (COX)-1-dependent production of thromboxane A2 (TXA2) in platelets and COX-2-dependent production of anti-aggregatory prostaglandin I2 (PGI2) in vessel walls, resulting in "aspirin dilemma." Our objective is to investigate whether ASP6537 can overcome aspirin dilemma and exert a potent antithrombotic effect without a concurrent ulcerogenic effect. We evaluated the inhibitory effects of ASP6537 on recombinant human COX-1 (rhCOX-1) and rhCOX-2 activities using a COX-1/2 selectivity test. To determine whether ASP6537 induces aspirin dilemma, we examined the effects of ASP6537 on in vitro TXA2 and PGI2 metabolite production from platelets and isolated aorta of guinea pigs, and on plasma concentrations of TXA2 and PGI2 metabolites in aged rats. Finally, we evaluated the antithrombotic effects and ulcerogenic activity of ASP6537 using an electrically induced carotid arterial thrombosis model and a gastric ulcer model in guinea pigs. The IC50 ratios of rhCOX-2 to rhCOX-1 for ASP6537 and aspirin were >142,000 and 1.63 fold, respectively. ASP6537 inhibited TXA2 production more selectively than aspirin in in vitro and in vivo TXA2/PGI2 production studies. ASP6537 exerted a significant antithrombotic effect at ≥3 mg/kg, while aspirin tended to inhibit thrombosis at 300 mg/kg but it was not statistically significant. Further, ASP6537 did not induce ulcer formation at 100 mg/kg, whereas aspirin exhibited an ulcerogenic effect at doses of ≥100 mg/kg. ASP6537 functions as a highly selective COX-1 inhibitor with a superior ability to aspirin for normalizing TXA2/PGI2 balance, and exerts antithrombotic effect without ulcerogenic effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

Low-levels of fluoride in plaque and saliva and their effects on the demineralisation and remineralisation of enamel; role of fluoride toothpastes.

PubMed

Lynch, R J M; Navada, R; Walia, R

2004-01-01

To summarise support for current consensus on the likely means by which fluoride toothpastes reduce caries and review some relevant studies of the effect of low levels of fluoride on the demineralisation and remineralisation of enamel. The major anti-caries effect of fluoride toothpastes is thought to result from small but protracted elevations in levels of fluoride in plaque and saliva. Fluoride incorporated into enamel systemically does not reduce enamel solubility sufficiently to exert an anti-caries effect. Fluoride has the potential to exert an anti-caries benefit largely through three mechanisms; inhibition of demineralisation, promotion of remineralisation and interference with bacterial growth and metabolism. However, the low levels of fluoride thought to influence caries are insufficient to have a significant effect via the latter mechanism. Thus reductions in caries resulting from the use of fluoride toothpastes can be linked to modification of the demineralisation/remineralisation balance by direct effects on dental mineral exerted topically by low levels of fluoride. Numerous in vitro studies have shown that low levels of fluoride, typical of those found after many hours in resting plaque and saliva, and resulting from the regular use of fluoride toothpastes, can have a profound effect on enamel demineralisation and remineralisation.

Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts.

PubMed

Micucci, Matteo; Malaguti, Marco; Toschi, Tullia Gallina; Di Lecce, Giuseppe; Aldini, Rita; Angeletti, Andrea; Chiarini, Alberto; Budriesi, Roberta; Hrelia, Silvana

2015-01-01

This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE), of a Hibiscus sabdariffa L. flower extract (HSE), and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs) to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals.

Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts

PubMed Central

Micucci, Matteo; Gallina Toschi, Tullia; Di Lecce, Giuseppe; Aldini, Rita; Angeletti, Andrea; Chiarini, Alberto

2015-01-01

This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE), of a Hibiscus sabdariffa L. flower extract (HSE), and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs) to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals. PMID:26180582

Pooling job physical exposure data from multiple independent studies in a consortium study of carpal tunnel syndrome

PubMed Central

Kapellusch, Jay M.; Garg, Arun; Bao, Stephen S.; Silverstein, Barbara A.; Burt, Susan E.; Dale, Ann Marie; Evanoff, Bradley A.; Gerr, Frederic E.; Harris-Adamson, Carisa; Hegmann, Kurt T.; Merlino, Linda A.; Rempel, David M.

2015-01-01

Pooling data from different epidemiological studies of musculoskeletal disorders (MSDs) is necessary to improve statistical power and to more precisely quantify exposure–response relationships for MSDs. The pooling process is difficult and time-consuming, and small methodological differences could lead to different exposure–response relationships. A subcommittee of a six-study research consortium studying carpal tunnel syndrome: (i) visited each study site, (ii) documented methods used to collect physical exposure data and (iii) determined compatibility of exposure variables across studies. Certain measures of force, frequency of exertion and duty cycle were collected by all studies and were largely compatible. A portion of studies had detailed data to investigate simultaneous combinations of force, frequency and duration of exertions. Limited compatibility was found for hand/wrist posture. Only two studies could calculate compatible Strain Index scores, but Threshold Limit Value for Hand Activity Level could be determined for all studies. Challenges of pooling data, resources required and recommendations for future researchers are discussed. PMID:23697792

Acoustic Interaction Forces and Torques Acting on Suspended Spheres in an Ideal Fluid.

PubMed

Lopes, J Henrique; Azarpeyvand, Mahdi; Silva, Glauber T

2016-01-01

In this paper, the acoustic interaction forces and torques exerted by an arbitrary time-harmonic wave on a set of N objects suspended in an inviscid fluid are theoretically analyzed. We utilize the partial-wave expansion method with translational addition theorem and re-expansion of multipole series to solve the related multiple scattering problem. We show that the acoustic interaction force and torque can be obtained using the farfield radiation force and torque formulas. To exemplify the method, we calculate the interaction forces exerted by an external traveling and standing plane wave on an arrangement of two and three olive-oil droplets in water. The droplets' radii are comparable to the wavelength (i.e., Mie scattering regime). The results show that the acoustic interaction forces present an oscillatory spatial distribution which follows the pattern formed by interference between the external and rescattered waves. In addition, acoustic interaction torques arise on the absorbing droplets whenever a nonsymmetric wavefront is formed by the external and rescattered waves' interference.

Cardiovascular Biology of the Incretin System

PubMed Central

Ussher, John R.; Drucker, Daniel J.

2012-01-01

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. Two classes of medications that enhance incretin action, GLP-1R agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus (T2DM). We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure and postprandial lipoprotein secretion. Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. Incretin-based agents control body weight, improve glycemic control with a low risk of hypoglycemia, decrease blood pressure, inhibit the secretion of intestinal chylomicrons, and reduce inflammation in preclinical studies. Nevertheless, there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease. Hence, a more complete understanding of the cardiovascular risk:benefit ratio of incretin-based therapies will require completion of long term cardiovascular outcome studies currently underway in patients with T2DM. PMID:22323472

Higher glucose levels associated with lower memory and reduced hippocampal microstructure.

PubMed

Kerti, Lucia; Witte, A Veronica; Winkler, Angela; Grittner, Ulrike; Rujescu, Dan; Flöel, Agnes

2013-11-12

For this cross-sectional study, we aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia. In 141 individuals (72 women, mean age 63.1 years ± 6.9 SD), memory was tested using the Rey Auditory Verbal Learning Test. Peripheral levels of fasting HbA1c, glucose, and insulin and 3-tesla MRI scans were acquired to assess hippocampal volume and microstructure, as indicated by gray matter barrier density. Linear regression and simple mediation models were calculated to examine associations among memory, glucose metabolism, and hippocampal parameters. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure. Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.

Occurrence and transport of tetracycline, sulfonamide, quinolone, and macrolide antibiotics in the Haihe River Basin, China.

PubMed

Luo, Yi; Xu, Lin; Rysz, Michal; Wang, Yuqiu; Zhang, Hao; Alvarez, Pedro J J

2011-03-01

The occurrence and transport of 12 antibiotics (from the tetracycline, sulfonamide, quinolone, and macrolide families) was studied in a 72-km stretch of the Haihe River, China, and in six of its tributaries. Aqueous and sediment samples were analyzed by HPLC-MS/MS. Sulfonamides were detected at the highest concentrations (24-385 ng/L) and highest frequencies (76-100%). Eight of the 12 antibiotics likely originated from veterinary applications in swine farms and fishponds, and concentrations at these sources (0.12-47 μg/L) were 1-2 orders of magnitude higher than in the effluent of local wastewater treatment plants. Sulfachloropyridazine (SCP) was detected in all swine farm and fishpond samples (maximum concentration 47 μg/L), which suggests its potential usefulness to indicate livestock source pollution in the Haihe River basin. Hydrological and chemical factors that may influence antibiotic distribution in the Haihe River were considered by multiple regression analysis. River flow rate exerted the most significant effect on the first-order attenuation coefficient (K) for sulfonamides, quinolones, and macrolides, with higher flow rates resulting in higher K, probably due to dilution. For tetracyclines, sediment total organic matter and cation exchange capacity exerted a greater impact on K than flow rate, indicating that adsorption to sediments plays an important role in attenuating tetracycline migration. Overall, the predominance of sulfonamides in the Haihe River underscores the need to consider regulating their veterinary use and improving the management and treatment of associated releases.

Meiotic recombination and spermatogenic impairment in Mus musculus domesticus carrying multiple simple Robertsonian translocations.

PubMed

Merico, V; Pigozzi, M I; Esposito, A; Merani, M S; Garagna, S

2003-01-01

We quantitatively analyzed the spermatogenic process, including evaluation of seminiferous tubules with defective cycles, rates of germ cell death and sperm morphology, in adult male mice with standard telocentric chromosomes (2n = 40, CD1 strain), homozygous (2n = 24, Mil II population) and heterozygous (2n = 24 x 40) for Robertsonian (Rb) rearrangements. The animals were analyzed at three different ages: three, five and seven months after birth. The number and position of crossover events were also determined by chiasmata counting and immunostaining with an antibody against mouse MLH1 protein. Our analysis of spermatogenesis confirms the impairment of the spermatogenic process in multiple simple heterozygotes due to both germ cell and abnormal sperm morphology. The detrimental effects exerted by Rb heterozygosities were found to be at least partially buffered with time: the frequency of defective tubules was lower and germ cell survival and sperm morphology better in 7-month-old animals than in the 3- and 5-month-old mice. While there are previously published data on germ cell death in multiple simple heterozygotes, this is the first report of a partial rescue of spermatogenesis with time. The mean frequency of MLH1 foci was lower in Rb homozygous and heterozygous mice than in mice carrying all telocentric chromosomes. The lower number of foci in Rb mice can be ascribed to a decrease in the number of multiple chiasmata and the maintenance of single chiasmata preferentially located in the terminal region of both the telocentric and metacentric chromosomes. Copyright 2003 S. Karger AG, Basel

The ethnobotany of psychoactive plant use: a phylogenetic perspective

PubMed Central

2016-01-01

Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests multiple ethnobotanical origins and widespread human dependence on these plants, motivating pharmacological investigation into their potential as modern therapeutics for various neurological disorders. PMID:27761334

The ethnobotany of psychoactive plant use: a phylogenetic perspective.

PubMed

Alrashedy, Nashmiah Aid; Molina, Jeanmaire

2016-01-01

Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests multiple ethnobotanical origins and widespread human dependence on these plants, motivating pharmacological investigation into their potential as modern therapeutics for various neurological disorders.

Lenalidomide consolidation treatment in patients with multiple myeloma suppresses myelopoieses but spares erythropoiesis.

PubMed

Wilk, Christian Matthias; Heinzler, Niklas; Boquoi, Amelie; Cadeddu, Ron-Patrick; Strapatsas, Tobias; Dienst, Ariane; Majidi, Fatemeh; Deenen, René; Bruns, Ingmar; Schroeder, Thomas; Köhrer, Karl; Haas, Rainer; Kobbe, Guido; Fenk, Roland

2016-11-15

New drugs for the treatment of multiple myeloma (MM) comprise immunomodulatory substances such as lenalidomide and related compounds. While lenalidomide has found its way into first-line treatment as well as into relapse therapy, little is known about lenalidomide effects on normal hematopoietic stem and progenitor cells (HSPCs). In this study, we investigated whether HSPCs are influenced by lenalidomide on a phenotypic, functional and gene expression level. For that purpose, samples from patients with MM were obtained who underwent equivalent first-line treatment including induction therapy, cytotoxic stem cell mobilization and high-dose melphalan therapy followed by autologous blood stem cell transplantation and a subsequent uniform lenalidomide consolidation treatment within a prospective clinical trial. We found that after six months of lenalidomide therapy, the number of CD34(+) HSPCs decreased. Additionally, lenalidomide affects the numerical composition of hematopoietic cells in the bone marrow while it does not affect long-term HSPC proliferation in vitro. We found a significant amplification of fetal hemoglobin (HbF) expression on a transcriptional level and can confirm a stimulated erythropoiesis on a phenotypic level. These effects were accompanied by silencing of the TGF-β signaling pathway on the gene expression and protein level that is known to be amplified in active MM. However, these pleiotropic effects gave no evidence for mutagenic potential. In conclusion, lenalidomide does not exert long-term effects on proliferation of HSPCs but instead promotes erythropoiesis by shifting hemoglobin expression toward HbF and by silencing the TGF-β signaling pathway. © 2016 UICC.

Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

PubMed Central

Geisbert, Joan B; Shedlock, Devon J; Xu, Ling; Lamoreaux, Laurie; Custers, Jerome H. H. V; Popernack, Paul M; Yang, Zhi-Yong; Pau, Maria G; Roederer, Mario; Koup, Richard A; Goudsmit, Jaap; Jahrling, Peter B; Nabel, Gary J

2006-01-01

Background Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. Methods and Findings To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 1010 particles, two logs lower than that used previously. Conclusions Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 1010 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate. PMID:16683867

Role of Obesity in Asthma: Mechanisms and Management Strategies.

PubMed

Scott, Hayley A; Wood, Lisa G; Gibson, Peter G

2017-08-01

Obesity is a commonly reported comorbidity in asthma, particularly in severe asthma. Obese asthmatics are highly symptomatic with a poor quality of life, despite using high-dose inhaled corticosteroids. While the clinical manifestations have been documented, the aetiologies of obese-asthma remain unclear. Several potential mechanisms have been proposed, including poor diet quality, physical inactivity and consequent accrual of excess adipose tissue. Each of these factors independently activates inflammatory pathways, potentially exerting effects in the airways. Because the origins of obesity are multifactorial, it is now believed there are multiple obese-asthma phenotypes, with varied aetiologies and clinical consequences. In this review, we will describe the clinical implications of obesity in people with asthma, our current understanding of the mechanisms driving this association and describe recently proposed obese-asthma phenotypes. We will then discuss how asthma management is complicated by obesity, and provide graded recommendations for the management of obesity in this population.

Development of, and initial validity evidence for, the referee self-efficacy scale: a multistudy report.

PubMed

Myers, Nicholas D; Feltz, Deborah L; Guillén, Félix; Dithurbide, Lori

2012-12-01

The purpose of this multistudy report was to develop, and then to provide initial validity evidence for measures derived from, the Referee Self-Efficacy Scale. Data were collected from referees (N = 1609) in the United States (n = 978) and Spain (n = 631). In Study 1 (n = 512), a single-group exploratory structural equation model provided evidence for four factors: game knowledge, decision making, pressure, and communication. In Study 2 (n = 1153), multiple-group confirmatory factor analytic models provided evidence for partial factorial invariance by country, level of competition, team gender, and sport refereed. In Study 3 (n = 456), potential sources of referee self-efficacy information combined to account for a moderate or large amount of variance in each dimension of referee self-efficacy with years of referee experience, highest level refereed, physical/mental preparation, and environmental comfort, each exerting at least two statistically significant direct effects.

Neurobiology of Schemas and Schema-Mediated Memory.

PubMed

Gilboa, Asaf; Marlatte, Hannah

2017-08-01

Schemas are superordinate knowledge structures that reflect abstracted commonalities across multiple experiences, exerting powerful influences over how events are perceived, interpreted, and remembered. Activated schema templates modulate early perceptual processing, as they get populated with specific informational instances (schema instantiation). Instantiated schemas, in turn, can enhance or distort mnemonic processing from the outset (at encoding), impact offline memory transformation and accelerate neocortical integration. Recent studies demonstrate distinctive neurobiological processes underlying schema-related learning. Interactions between the ventromedial prefrontal cortex (vmPFC), hippocampus, angular gyrus (AG), and unimodal associative cortices support context-relevant schema instantiation and schema mnemonic effects. The vmPFC and hippocampus may compete (as suggested by some models) or synchronize (as suggested by others) to optimize schema-related learning depending on the specific operationalization of schema memory. This highlights the need for more precise definitions of memory schemas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sandalwood Album Oil as a Botanical Therapeutic in Dermatology

PubMed Central

Levenson, Corey

2017-01-01

Many skin conditions and diseases are characterized by inflammation, infection, and hyperplasia. Safe and effective topical treatment options that can be used long-term are needed. Traditional botanical medicines, which are often complex mixtures that exert their biological activities via multiple mechanisms of action, are being studied as potential new active ingredients in dermatology. Sandalwood album oil (SAO), also known as East Indian sandalwood oil (EISO), is an essential oil distilled from the Santalum album tree and has demonstrated biological activity as an anti-inflammatory, anti-microbial, and anti-proliferative agent. Sandalwood album oil has also shown promise in clinical trials for treatment of acne, psoriasis, eczema, common warts, and molluscum contagiosum. The favorable safety profile, ease of topical use, and recent availability of pharmaceutical-grade sandalwood album oil support its broader use as the basis of novel therapies in dermatology. PMID:29344319

Structural basis for the antifolding activity of a molecular chaperone

NASA Astrophysics Data System (ADS)

Huang, Chengdong; Rossi, Paolo; Saio, Tomohide; Kalodimos, Charalampos G.

2016-09-01

Molecular chaperones act on non-native proteins in the cell to prevent their aggregation, premature folding or misfolding. Different chaperones often exert distinct effects, such as acceleration or delay of folding, on client proteins via mechanisms that are poorly understood. Here we report the solution structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. SecB uses long hydrophobic grooves that run around its disk-like shape to recognize and bind to multiple hydrophobic segments across the length of non-native proteins. The multivalent binding mode results in proteins wrapping around SecB. This unique complex architecture alters the kinetics of protein binding to SecB and confers strong antifolding activity on the chaperone. The data show how the different architectures of chaperones result in distinct binding modes with non-native proteins that ultimately define the activity of the chaperone.

The positive relationship between ocean acidification and pollution.

PubMed

Zeng, Xiangfeng; Chen, Xijuan; Zhuang, Jie

2015-02-15

Ocean acidification and pollution coexist to exert combined effects on the functions and services of marine ecosystems. Ocean acidification can increase the biotoxicity of heavy metals by altering their speciation and bioavailability. Marine pollutants, such as heavy metals and oils, could decrease the photosynthesis rate and increase the respiration rate of marine organisms as a result of biotoxicity and eutrophication, facilitating ocean acidification to varying degrees. Here we review the complex interactions between ocean acidification and pollution in the context of linkage of multiple stressors to marine ecosystems. The synthesized information shows that pollution-affected respiration acidifies coastal oceans more than the uptake of anthropogenic carbon dioxide. Coastal regions are more vulnerable to the negative impact of ocean acidification due to large influxes of pollutants from terrestrial ecosystems. Ocean acidification and pollution facilitate each other, and thus coastal environmental protection from pollution has a large potential for mitigating acidification risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improved ethanol production at high temperature by consolidated bioprocessing using Saccharomyces cerevisiae strain engineered with artificial zinc finger protein.

PubMed

Khatun, M Mahfuza; Yu, Xinshui; Kondo, Akihiko; Bai, Fengwu; Zhao, Xinqing

2017-12-01

In this work, the consolidated bioprocessing (CBP) yeast Saccharomyces cerevisiae MNII/cocδBEC3 was transformed by an artificial zinc finger protein (AZFP) library to improve its thermal tolerance, and the strain MNII-AZFP with superior growth at 42°C was selected. Improved degradation of acid swollen cellulose by 45.9% led to an increase in ethanol production, when compared to the control strain. Moreover, the fermentation of Jerusalem artichoke stalk (JAS) by MNII-AZFP was shortened by 12h at 42°C with a concomitant improvement in ethanol production. Comparative transcriptomics analysis suggested that the AZFP in the mutant exerted beneficial effect by modulating the expression of multiple functional genes. These results provide a feasible strategy for efficient ethanol production from JAS and other cellulosic biomass through CBP based-fermentation at elevated temperatures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of various treatments on the chemokinetic behavior of third-stage larvae of Strongyloides ratti on a sodium chloride gradient.

PubMed

Tobata-Kudo, H; Higo, H; Koga, M; Tada, I

2000-11-01

In observations of the movements of the infective third-stage larvae of a rodent parasitic nematode, Strongyloides ratti, on a sodium chloride gradient set up on agarose plates, two types of chemokinetic behavior were seen: a unidirectional avoidance movement on initial placement of the larvae in unfavorable environmental conditions and a random dispersal movement on their placement within an area of favorable conditions. Track patterns were straight in the avoidance movement but included multiple changes of direction and loops in the dispersal movement. In the present study we examined the interventional activity of treatment with various enzymes, lectins, and chemicals by analyzing the unidirectional avoidance movements of the larvae. We observed that beta-glucosidase, hyaluronidase, beta-galactosidase, trypsin, protease, lipase, phospholipase C, soybean agglutinin, wheat germ agglutinin, and spermidine exerted inhibitory actions on those movements, which may be guided by the chemosensory function of this nematode.

OCA-B regulation of B-cell development and function.

PubMed

Teitell, Michael A

2003-10-01

The transcriptional co-activator OCA-B [for Oct co-activator from B cells, also known as OBF-1 (OCT-binding factor-1) and Bob1] is not required for B-cell genesis but does regulate subsequent B-cell development and function. OCA-B deficient mice show strain-specific, partial blocks at multiple stages of B-cell maturation and a complete disruption of germinal center formation in all strains, causing humoral immune deficiency and susceptibility to infection. OCA-B probably exerts its effects through the regulation of octamer-motif controlled gene expression. The OCA-B gene encodes two proteins of distinct molecular weight, designated p34 and p35. The p34 isoform localizes in the nucleus, whereas the p35 isoform is myristoylated and is bound to the cytoplasmic membrane. p35 can traffic to the nucleus and probably activates octamer-dependent transcription, although this OCA-B isoform might regulate B cells through membrane-related signal transduction.

Permeability of the blood-brain barrier to the neurotensin8-13 analog NT1.

PubMed

Banks, W A; Wustrow, D J; Cody, W L; Davis, M D; Kastin, A J

1995-10-09

Neurotensin (NT) has been suggested to be a neuropeptide with therapeutic potential. We used multiple-time regression analysis to measure the unidirectional influx constant (Ki) of a tritiated analog of NT8-13, NT1, with improved metabolic stability. The Ki of [3H]NT1 across the blood-brain barrier (BBB) was 5.12(10(-4)) ml/g-min and was decreased 66% by unlabeled NT1 system. The amount of NT1 crossing the BBB, 0.087% of the injected dose per gram of brain, is consistent with its exerting central effects after peripheral administration. The stable [3H]NT1 crossed the BBB in intact form as assessed by HPLC and completely crossed the endothelial cells that comprise the BBB as assessed by the capillary depletion method. The presence of a transport system could be important for the development of NT analogs.

A factor influence study of trace element bioaccumulation in moss bags.

PubMed

Cesa, M; Campisi, B; Bizzotto, A; Ferraro, C; Fumagalli, F; Nimis, P L

2008-10-01

Moss bags of Rhynchostegium riparioides were exposed to different water concentrations of 11 trace elements under laboratory conditions, according to a saturated fractional factorial design (67 treated combinations), with the aim of measuring (1) element uptake and (2) the main effects and first-order interactions of influent factors. Bioaccumulation was directly proportional to water concentration, but the uptake ratio (ranging from 10(2) to 10(5)) also depended on the concentration of other metals. The highest uptake ratios were observed for Al, Cu, Cr, Hg, and Pb. The multiple regression model showed that interactions among elements exist and induce both antagonism (Fe is the most frequent competitor) and synergism (Cr exerts a great influence on Pb and Zn uptake). Interactions might be relatively strong (as for As, Cr, and Pb) or weak (Cd and Hg). This evidence should be taken into consideration in biomonitoring surveys of industrial sites, where effluents release more than one contaminant.

Advance and Retreat: Tobacco Control Policy in the U.S. Military

PubMed Central

Arvey, Sarah R.; Malone, Ruth E.

2009-01-01

This archival study explored why military tobacco control initiatives have thus far largely failed to meet their goals. We analyzed more than 5,000 previously undisclosed internal tobacco industry documents made public via an online database and additional documents obtained from the U.S. military. In four case studies, we illustrate how pressures exerted by multiple political actors resulted in weakening or rescinding military tobacco control policy initiatives. Our findings suggest that lowering military smoking rates will require health policymakers to better anticipate and counter political opponents. The findings also suggest that effective tobacco control policies may require strong, explicit implementation instructions and high-level Department of Defense support. Finally, policy designers should also consider ways to reduce or eliminate existing perverse incentives to increase tobacco consumption, such as allowing exchange store tobacco sales to fund Morale, Recreation, and Welfare Programs. PMID:19160617

One-year enzyme-linked immunosorbent assay follow-up of human interleukin for Da cells/leukemia inhibitory factor in blood and urine of 22 kidney transplant recipients.

PubMed

Morel, D; Taupin, J L; Combe, C; Potaux, L; Gualde, N; Moreau, J F

1994-12-15

The cytokine human interleukin for Da cells/leukemia inhibitory factor (HILDA/LIF) exerts multiple biological effects in vitro. In mice, high circulating levels of HILDA/LIF induce a wide range of pathophysiological events, some of them closely involved with immunological and inflammatory responses. Using a sandwich ELISA recognizing the natural human HILDA/LIF molecule with a threshold of 50 pg/ml in urine and 150 pg/ml in plasma, we monitored the urine and plasma HILDA/LIF levels of 22 patients in their first year after a kidney transplant. HILDA/LIF urine excretion is increased during acute rejection, and infections also trigger heavy HILDA/LIF plasma concentrations or urine excretion. In addition, this study raises the question of HILDA/LIF involvement in post-kidney-transplant phenomena such as hypercalcemia, osteoporosis, or the reversal of anemia.

Exosomes Function in Tumor Immune Microenvironment.

PubMed

Huang, Yin; Liu, Keli; Li, Qing; Yao, Yikun; Wang, Ying

2018-01-01

Immune cells and mesenchymal stem/stromal cells are the major cellular components in tumor microenvironment that actively migrate to tumor sites by sensing "signals" released from tumor cells. Together with other stromal cells, they form the soil for malignant cell progression. In the crosstalk between tumor cells and its surrounded microenvironment, exosomes exert multiple functions in shaping tumor immune responses. In tumor cells, their exosomes can lead to pro-tumor immune responses, whereas in immune cells, their derived exosomes can operate on tumor cells and regulate their ability to growth, metastasis, even reaction to chemotherapy. Employing exosomes as vehicles for the delivery products to initiate anti-tumor immune responses has striking therapeutic effects on tumor progression. Thus, exosomes are potential therapeutic targets in tumor-related clinical conditions. Here we discuss the role of exosomes in regulating tumor immune microenvironment and future indications for the clinical application of exosomes.

The role of proteomics in studies of protein moonlighting.

PubMed

Beynon, Robert J; Hammond, Dean; Harman, Victoria; Woolerton, Yvonne

2014-12-01

The increasing acceptance that proteins may exert multiple functions in the cell brings with it new analytical challenges that will have an impact on the field of proteomics. Many proteomics workflows begin by destroying information about the interactions between different proteins, and the reduction of a complex protein mixture to constituent peptides also scrambles information about the combinatorial potential of post-translational modifications. To bring the focus of proteomics on to the domain of protein moonlighting will require novel analytical and quantitative approaches.

Dynamical Evolution and Spin-Orbit Resonances of Potentially Habitable Exoplanets. The Case of GJ 667C

DTIC Science & Technology

2014-01-10

observed trend is consistent with a gravitational acceleration exerted by the inner pair of stars (A and B) in this multiple star system. Our planet...the other hand, the observed trend in the RV of the C component can be caused by its orbital acceleration around the AB pair. 3. LONG-TERM EVOLUTION...polar torque acting on a rotating planet is the sum of the gravitational torque, caused by the triaxial permanent shape and the corresponding quadrupole

Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice

PubMed Central

Brandon-Warner, Elizabeth; Eheim, Ashley L; Foureau, David M; Walling, Tracy L; Schrum, Laura W; McKillop, Iain H

2012-01-01

Hepatocellular carcinoma (HCC) is a global health burden with limited treatment options and poor prognosis. Silibinin, an antioxidant derived from the Milk Thistle plant (Silybum marianum), is reported to exert hepatoprotective and antitumorigenic effects in vitro and in vivo by suppressing oxidative stress and proliferation. Using a DEN-initiated mouse model of HCC, this study examined the effects of dietary silibinin supplementation alone, or in combination with chronic ethanol consumption on HCC progression. Our data demonstrate silibinin exerted marginal hepatoprotective effects in early stages of hepatocarcinogenesis but, when co-administered with ethanol, exacerbated the promotional effects of ethanol in HCC bearing mice, but only in males. PMID:22863537

Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice.

PubMed

Brandon-Warner, Elizabeth; Eheim, Ashley L; Foureau, David M; Walling, Tracy L; Schrum, Laura W; McKillop, Iain H

2012-12-29

Hepatocellular carcinoma (HCC) is a global health burden with limited treatment options and poor prognosis. Silibinin, an antioxidant derived from the Milk Thistle plant (Silybum marianum), is reported to exert hepatoprotective and antitumorigenic effects in vitro and in vivo by suppressing oxidative stress and proliferation. Using a DEN-initiated mouse model of HCC, this study examined the effects of dietary silibinin supplementation alone, or in combination with chronic ethanol consumption on HCC progression. Our data demonstrate silibinin exerted marginal hepatoprotective effects in early stages of hepatocarcinogenesis but, when co-administered with ethanol, exacerbated the promotional effects of ethanol in HCC bearing mice, but only in males. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A trait-based framework for stream algal communities.

PubMed

Lange, Katharina; Townsend, Colin Richard; Matthaei, Christoph David

2016-01-01

The use of trait-based approaches to detect effects of land use and climate change on terrestrial plant and aquatic phytoplankton communities is increasing, but such a framework is still needed for benthic stream algae. Here we present a conceptual framework of morphological, physiological, behavioural and life-history traits relating to resource acquisition and resistance to disturbance. We tested this approach by assessing the relationships between multiple anthropogenic stressors and algal traits at 43 stream sites. Our "natural experiment" was conducted along gradients of agricultural land-use intensity (0-95% of the catchment in high-producing pasture) and hydrological alteration (0-92% streamflow reduction resulting from water abstraction for irrigation) as well as related physicochemical variables (total nitrogen concentration and deposited fine sediment). Strategic choice of study sites meant that agricultural intensity and hydrological alteration were uncorrelated. We studied the relationships of seven traits (with 23 trait categories) to our environmental predictor variables using general linear models and an information-theoretic model-selection approach. Life form, nitrogen fixation and spore formation were key traits that showed the strongest relationships with environmental stressors. Overall, FI (farming intensity) exerted stronger effects on algal communities than hydrological alteration. The large-bodied, non-attached, filamentous algae that dominated under high farming intensities have limited dispersal abilities but may cope with unfavourable conditions through the formation of spores. Antagonistic interactions between FI and flow reduction were observed for some trait variables, whereas no interactions occurred for nitrogen concentration and fine sediment. Our conceptual framework was well supported by tests of ten specific hypotheses predicting effects of resource supply and disturbance on algal traits. Our study also shows that investigating a fairly comprehensive set of traits can help shed light on the drivers of algal community composition in situations where multiple stressors are operating. Further, to understand non-linear and non-additive effects of such drivers, communities need to be studied along multiple gradients of natural variation or anthropogenic stressors.

Effect of Dietary Purified Xanthohumol from Hop (Humulus lupulus L.) Pomace on Adipose Tissue Mass, Fasting Blood Glucose Level, and Lipid Metabolism in KK-Ay Mice.

PubMed

Takahashi, Koki; Osada, Kyoichi

2017-05-01

We previously showed that xanthohumol-rich hop extract (XRHE, ~18% xanthohumol) exerts anti-obesity effects in rats fed a high-fat diet through regulation of fatty acid metabolism. In this study, we examined the effects of dietary purified xanthohumol from XRHE (PX, ~91.9% xanthohumol) in KK-Ay mice in order to understand the anti-obesity effects of xanthohumol alone because XRHE contains 82% unknown compounds. Dietary consumption of PX significantly inhibited an increase in the visceral fat weight of mice compared to those fed control diet without PX. Plasma leptin level was significantly lower in the PX-fed group than in the control group. Dietary PX lowered hepatic fatty acid synthesis by down-regulation of SREBP1c mRNA expression in the liver. On the other hand, fatty acid β-oxidation in the liver was promoted by dietary PX through the up-regulation of PPARα mRNA expression. Moreover, the fecal levels of fatty acids and carbohydrates increased by dietary PX. PX inhibited lipase or α-amylase activity in vitro. Thus, we found that PX may exert anti-obesity effects through the regulation of lipid metabolism and inhibition of intestinal fat and carbohydrate absorption, and that xanthohumol alone may exert anti-obesity effects.

Antifungal activity and cytotoxicity of extracts and triterpenoid saponins obtained from the aerial parts of Anagallis arvensis L.

PubMed

Soberón, José R; Sgariglia, Melina A; Pastoriza, Ana C; Soruco, Estela M; Jäger, Sebastián N; Labadie, Guillermo R; Sampietro, Diego A; Vattuone, Marta A

2017-05-05

Anagallis arvensis L. (Primulaceae) is used in argentinean northwestern traditional medicine to treat fungal infections. We are reporting the isolation and identification of compounds with antifungal activity against human pathogenic yeast Candida albicans, and toxicity evaluation. to study the antifungal activity of extracts and purified compounds obtained form A. arvensis aerial parts, alone and in combinations with fluconazole (FLU), and to study the toxicity of the active compounds. Disk diffusion assays were used to perform an activity-guided isolation of antifungal compounds from the aerial parts of A. arvensis. Broth dilution checkerboard and viable cell count assays were employed to determine the effects of samples and combinations of FLU + samples against Candida albicans. The chemical structures of active compounds were elucidated by spectroscopic analysis. Genotoxic and haemolytic effects of the isolated compounds were determined. Four triterpenoid saponins (1-4) were identified. Anagallisin C (AnC), exerted the highest inhibitory activity among the assayed compounds against C. albicans reference strain (ATCC 10231), with MIC-0 =1µg/mL. The Fractional Inhibitory Concentration Index (FICI=0.129) indicated a synergistic effect between AnC (0.125µg/mL) and FLU (0.031µg/mL) against C. albicans ATCC 10231. AnC inhibited C. albicans 12-99 FLU resistant strain (MIC-0 =1µg/mL), and the FICI=0.188 indicated a synergistic effect between AnC (0.125µg/mL) and fluconazole (16µg/mL). The combination AnC+ FLU exerted fungicidal activity against both C. albicans strains. AnC exerted inhibitory activity against C. albicans ATCC 10231 sessile cells (MIC 5 0=0.5µg/mL and MIC 80 =1µg/mL) and against C. albicans 12-99 sessile cells (MIC 5 0=0.75µg/mL and MIC 80 =1.25µg/mL). AnC exerted haemolytic effect against human red blood cells at 15µg/mL and did not exerted genotoxic effect on Bacillus subtilis rec strains. The antifungal activity and lack of genotoxic effects of AnC give support to the traditional use of A. arvensis as antifungal and makes AnC a compound of interest to expand the available antifungal drugs. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Interest Group Conflict Over Medicaid Expansion: The Surprising Impact of Public Advocates

PubMed Central

Callaghan, Timothy

2016-01-01

Objectives. We examined the potential economic, policy, and political influences on the decisions of the 50 US states to expand Medicaid under the Affordable Care Act. Methods. We related a measure of relative state progress toward Medicaid expansion updated to 2015 to each state’s economic circumstances, established policy frameworks in states, partisan control of state government, and lobbyists for businesses, medical professionals, unions, and public interest organizations. Results. The 9201 lobbyists working on health care reform in state capitols exerted a strong and significant impact on Medicaid expansion. Controlling for confounding factors (including partisanship and existing policy frameworks), we found that business and professional lobbyists exerted a negative effect on state Medicaid expansion and, unexpectedly, that public interest advocates exerted a positive effect. Conclusions. There are 3.1 million adults who lack coverage because they live in the 20 states that refused to expand Medicaid. Although political party and lobbyists for private interests present significant barriers in these states, legislative lobbying on behalf of the uninsured appears likely to be effective. PMID:26691109

The effect of firefighter protective garments, self-contained breathing apparatus and exertion in the heat on postural sway.

PubMed

White, Scott C; Hostler, David

2017-08-01

Fire suppression wearing thermal protective clothing (TPC) and self-contained breathing apparatus (SCBA) challenges a firefighter's balance and may explain firefighter falls. Postural control based on force plate centre of pressure (COP) was compared for healthy subjects wearing TPC and SCBA before and after 20 min of heavy physical exertion in hot conditions. Baseline measures with and without TPC and SCBA (two different SCBA cylinder masses) were compared before and after exertion that included elements of fire suppression activities in an environmental chamber. COP excursion and variability increased with exertion for TPC and SCBA conditions compared to non-stressed conditions. The two different cylinder masses had no significant effect. Wearing TPC and SCBA when physically stressed in a hot environment increases postural sway and exacerbates postural control. Subjects compensated for the extra mass and adjusted to control postural sway with the addition of TPC and SCBA, but the stress protocol amplified these adjustments. Practitioner Summary: Firefighters wear thermal protective clothing (TPC) and self-contained breathing apparatus (SCBA) when heat-stressed and fatigued. Wearing TPC and SCBA was found to negatively impact balance when stressed, but not for non-stressed or two different sized SCBA tanks. Simulating fire-ground conditions wearing TPC and SCBA should be considered for improving balance.

Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection.

PubMed

Koh, Eun-Kyoung; Yun, Woo-Bin; Kim, Ji-Eun; Song, Sung-Hwa; Sung, Ji-Eun; Lee, Hyun-Ah; Seo, Eun-Ji; Jee, Seung-Wan; Bae, Chang-Joon; Hwang, Dae-Youn

2016-06-01

To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Aβ-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Aβ-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Aβ-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75(NTR) expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis.

Beneficial effect of diosgenin as a stimulator of NGF on the brain with neuronal damage induced by Aβ-42 accumulation and neurotoxicant injection

PubMed Central

Koh, Eun-Kyoung; Yun, Woo-Bin; Kim, Ji-Eun; Song, Sung-Hwa; Sung, Ji-Eun; Lee, Hyun-Ah; Seo, Eun-Ji; Jee, Seung-Wan

2016-01-01

To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Aβ-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Aβ-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Aβ-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75NTR expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis. PMID:27382379

Signaling through three chemokine receptors triggers the migration of transplanted neural precursor cells in a model of multiple sclerosis.

PubMed

Cohen, Mikhal E; Fainstein, Nina; Lavon, Iris; Ben-Hur, Tamir

2014-09-01

Multiple sclerosis (MS) is a multifocal disease, and precursor cells need to migrate into the multiple lesions in order to exert their therapeutic effects. Therefore, cell migration is a crucial element in regenerative processes in MS, dictating the route of delivery, when cell transplantation is considered. We have previously shown that inflammation triggers migration of multi-potential neural precursor cells (NPCs) into the white matter of experimental autoimmune encephalomyelitis (EAE) rodents, a widely used model of MS. Here we investigated the molecular basis of this attraction. NPCs were grown from E13 embryonic mouse brains and transplanted into the lateral cerebral ventricles of EAE mice. Transplanted NPC migration was directed by three tissue-derived chemokines. Stromal cell-derived factor-1α, monocyte chemo-attractant protein-1 and hepatocyte growth factor were expressed in the EAE brain and specifically in microglia and astrocytes. Their cognate receptors, CXCR4, CCR2 or c-Met were constitutively expressed on NPCs. Selective blockage of CXCR4, CCR2 or c-Met partially inhibited NPC migration in EAE brains. Blocking all three receptors had an additive effect and resulted in profound inhibition of NPC migration, as compared to extensive migration of control NPCs. The inflammation-triggered NPC migration into white matter tracts was dependent on a motile NPC phenotype. Specifically, depriving NPCs from epidermal growth factor (EGF) prevented the induction of glial commitment and a motile phenotype (as indicated by an in vitro motility assay), hampering their response to neuroinflammation. In conclusion, signaling via three chemokine systems accounts for most of the inflammation-induced, tissue-derived attraction of transplanted NPCs into white matter tracts during EAE. Copyright © 2014. Published by Elsevier B.V.

Myricetin down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B.

PubMed

Lee, Kyung Mi; Kang, Nam Joo; Han, Jin Hee; Lee, Ki Won; Lee, Hyong Joo

2007-11-14

Abnormal expression of cyclooxygenase-2 (COX-2) has been implicated in the development of cancer. There are multiple lines of evidence that red wine exerts chemopreventive effects, and 3,5,4'-trihydroxy- trans-stilbene (resveratrol), which is a non-flavonoid polyphenol found in red wine, has been reported to be a natural chemopreventive agent. However, other phytochemicals might contribute to the cancer-preventive activities of red wine, and the flavonol content of red wines is about 30 times higher than that of resveratrol. Here we report that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, inhibits 12-O-tetradecanoylphorbol-13-acetate (phorbol ester)-induced COX-2 expression in JB6 P+ mouse epidermal (JB6 P+) cells by suppressing activation of nuclear factor kappa B (NF-kappaB). Myricetin at 10 and 20 microM inhibited phorbol ester-induced upregulation of COX-2 protein, while resveratrol at the same concentration did not exert significant effects. The phorbol ester-induced production of prostaglandin E 2 was also attenuated by myricetin treatment. Myricetin inhibited both COX-2 and NF-kappaB transactivation in phorbol ester-treated JB6 P+ cells, as determined using a luciferase assay. Myricetin blocked the phorbol ester-stimulated DNA binding activity of NF-kappaB, as determined using an electrophoretic mobility shift assay. Moreover, TPCK (N-tosyl-l-phenylalanine chloromethyl ketone), a NF-kappaB inhibitor, significantly attenuated COX-2 expression and NF-kappaB promoter activity in phorbol ester-treated JB6 P+ cells. In addition, red wine extract inhibited phorbol ester-induced COX-2 expression and NF-kappaB transactivation in JB6 P+ cells. Collectively, these data suggest that myricetin contributes to the chemopreventive effects of red wine through inhibition of COX-2 expression by blocking the activation of NF-kappaB.

Effect of 1,3-1,6 β-Glucan on Natural and Experimental Deformed Wing Virus Infection in Newly Emerged Honeybees (Apis mellifera ligustica)

PubMed Central

Sagona, Simona; Carrozza, Maria Luisa; Forzan, Mario; Pizzurro, Federica; Bibbiani, Carlo; Miragliotta, Vincenzo; Abramo, Francesca; Millanta, Francesca; Bagliacca, Marco; Poli, Alessandro; Felicioli, Antonio

2016-01-01

The Western Honeybee is a key pollinator for natural as well as agricultural ecosystems. In the last decade massive honeybee colony losses have been observed worldwide, the result of a complex syndrome triggered by multiple stress factors, with the RNA virus Deformed Wing Virus (DWV) and the mite Varroa destructor playing crucial roles. The mite supports replication of DWV to high titers, which exert an immunosuppressive action and correlate with the onset of the disease. The aim of this study was to investigate the effect of 1,3–1,6 β-glucan, a natural innate immune system modulator, on honeybee response to low-titer natural and high-titer experimental DWV infection. As the effects exerted by ß-glucans can be remarkably different, depending on the target organism and the dose administered, two parallel experiments were performed, where 1,3–1,6 ß-glucan at a concentration of 0.5% and 2% respectively, was added to the diet of three cohorts of newly emerged honeybees, which were sampled from a Varroa-free apiary and harboured a low endogenous DWV viral titer. Each cohort was subjected to one of the following experimental treatments: no injection, injection of a high-copy number DWV suspension into the haemocel (experimental DWV infection) or injection of PBS into the haemocoel (physical injury). Control bees fed a ß-glucan-free diet were subjected to the same treatments. Viral load, survival rate, haemocyte populations and phenoloxidase activity of each experimental group were measured and compared. The results indicated that oral administration of 0.5% ß-glucan to naturally infected honeybees was associated with a significantly decrease of the number of infected bees and viral load they carried, and with a significant increase of the survival rate, suggesting that this natural immune modulator molecule might contribute to increase honeybee resistance to viral infection. PMID:27829027

A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial

PubMed Central

Rolland, M.; Magaret, C.A.; Rademeyer, C.; Fiore-Gartland, A.; Edlefsen, P.T.; DeCamp, A.; Ahmed, H.; Ngandu, N.; Larsen, B.B.; Frahm, N.; Marais, J.; Thebus, R.; Geraghty, D.; Hural, J.; Corey, L.; Kublin, J.; Gray, G.; McElrath, M.J.; Mullins, J.I.; Gilbert, P.B.; Williamson, C.

2016-01-01

Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A*02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes. PMID:27756485

Clinical application of the cardioprotective effects of volatile anaesthetics: PRO--get an extra benefit from a proven anaesthetic free of charge.

PubMed

Bein, Berthold

2011-09-01

Volatile anaesthetic agents have been used in millions of patients around the world and have proved to be both well tolerated and efficient. In recent years, cardioprotective properties of these drugs have been demonstrated unequivocally in numerous experimental investigations, but the beneficial effects of volatile anaesthetics in daily clinical practice are still under debate. In order to elucidate their cardioprotective properties in an unbiased way, the STAIR (Stroke Therapy Academic Industry Roundtable Preclinical Recommendation) criteria proposed as a framework for researchers in the field of neuroprotection can be applied to research conducted in the field of cardioprotection by volatile anaesthetics. All STAIR criteria have already been clearly fulfilled when all experimental and clinical studies are considered. Specifically, a dose-response pattern has been found with a minimal alveolar concentration value and a ceiling effect; volatile anaesthetics show two distinct therapeutic windows after application; important outcome measures such as hospital length of stay have been addressed; and multiple species have been studied by different independent groups of researchers who were largely able to reproduce their findings. Given the numerous confounding factors capable of attenuating or even abolishing the cardioprotective properties of volatile anaesthetics in laboratory investigations, the positive effects found in the majority of clinical trials point to the fact that the cardioprotective effects exerted by volatile anaesthetics are robust and triggered by interactions with several distinct cellular and subcellular targets, thereby providing multiplication and reiteration. The available evidence indicates that volatile anaesthetic agents should be used routinely in clinical practice in order to claim an extra benefit for our patients 'free of charge'.

Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity.

PubMed

Lee, Mi-Jeong; Pramyothin, Pornpoj; Karastergiou, Kalypso; Fried, Susan K

2014-03-01

Central obesity is associated with insulin resistance and dyslipidemia. Thus, the mechanisms that control fat distribution and its impact on systemic metabolism have importance for understanding the risk for diabetes and cardiovascular disease. Hypercortisolemia at the systemic (Cushing's syndrome) or local levels (due to adipose-specific overproduction via 11β-hydroxysteroid dehydrogenase 1) results in the preferential expansion of central, especially visceral fat depots. At the same time, peripheral subcutaneous depots can become depleted. The biochemical and molecular mechanisms underlying the depot-specific actions of glucocorticoids (GCs) on adipose tissue function remain poorly understood. GCs exert pleiotropic effects on adipocyte metabolic, endocrine and immune functions, and dampen adipose tissue inflammation. GCs also regulate multiple steps in the process of adipogenesis. Acting synergistically with insulin, GCs increase the expression of numerous genes involved in fat deposition. Variable effects of GC on lipolysis are reported, and GC can improve or impair insulin action depending on the experimental conditions. Thus, the net effect of GC on fat storage appears to depend on the physiologic context. The preferential effects of GC on visceral adipose tissue have been linked to higher cortisol production and glucocorticoid receptor expression, but the molecular details of the depot-dependent actions of GCs are only beginning to be understood. In addition, increasing evidence underlines the importance of circadian variations in GCs in relationship to the timing of meals for determining their anabolic actions on the adipocyte. In summary, although the molecular mechanisms remain to be fully elucidated, there is increasing evidence that GCs have multiple, depot-dependent effects on adipocyte gene expression and metabolism that promote central fat deposition. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

The Effects of Supplementation with a Vitamin and Mineral Complex with Guaraná Prior to Fasted Exercise on Affect, Exertion, Cognitive Performance, and Substrate Metabolism: A Randomized Controlled Trial.

PubMed

Veasey, Rachel C; Haskell-Ramsay, Crystal F; Kennedy, David O; Wishart, Karl; Maggini, Silvia; Fuchs, Caspar J; Stevenson, Emma J

2015-07-27

Exercise undertaken in a fasted state can lead to higher post-exercise mental fatigue. The administration of a vitamin and mineral complex with guaraná (MVM + G) has been shown to attenuate mental fatigue and improve performance during cognitively demanding tasks. This placebo-controlled, double-blind, randomized, balanced cross-over study examined the effect of MVM + G consumed prior to morning exercise on cognitive performance, affect, exertion, and substrate metabolism. Forty active males (age 21.4 ± 3.0 year; body mass index (BMI) 24.0 ± 2.4 kg/m2; maximal oxygen consumption (V̇O2max) 57.6 ± 7.3 mL/min/kg) completed two main trials, consuming either MVM + G or placebo prior to a 30-min run at 60% V̇O2max. Supplementation prior to exercise led to a small but significant reduction in Rating of Perceived Exertion (RPE) during exercise compared to the placebo. The MVM + G combination also led to significantly increased accuracy of numeric working memory and increased speed of picture recognition, compared to the placebo. There were no significant effects of supplementation on any other cognitive or mood measures or on substrate metabolism during exercise. These findings demonstrate that consuming a vitamin and mineral complex containing guaraná, prior to exercise, can positively impact subsequent memory performance and reduce perceived exertion during a moderate-intensity run in active males.

The Effects of Supplementation with a Vitamin and Mineral Complex with Guaraná Prior to Fasted Exercise on Affect, Exertion, Cognitive Performance, and Substrate Metabolism: A Randomized Controlled Trial

PubMed Central

Veasey, Rachel C.; Haskell-Ramsay, Crystal F.; Kennedy, David O.; Wishart, Karl; Maggini, Silvia; Fuchs, Caspar J.; Stevenson, Emma J.

2015-01-01

Exercise undertaken in a fasted state can lead to higher post-exercise mental fatigue. The administration of a vitamin and mineral complex with guaraná (MVM + G) has been shown to attenuate mental fatigue and improve performance during cognitively demanding tasks. This placebo-controlled, double-blind, randomized, balanced cross-over study examined the effect of MVM + G consumed prior to morning exercise on cognitive performance, affect, exertion, and substrate metabolism. Forty active males (age 21.4 ± 3.0 year; body mass index (BMI) 24.0 ± 2.4 kg/m2; maximal oxygen consumption (V̇O2max) 57.6 ± 7.3 mL/min/kg) completed two main trials, consuming either MVM + G or placebo prior to a 30-min run at 60% V̇O2max. Supplementation prior to exercise led to a small but significant reduction in Rating of Perceived Exertion (RPE) during exercise compared to the placebo. The MVM + G combination also led to significantly increased accuracy of numeric working memory and increased speed of picture recognition, compared to the placebo. There were no significant effects of supplementation on any other cognitive or mood measures or on substrate metabolism during exercise. These findings demonstrate that consuming a vitamin and mineral complex containing guaraná, prior to exercise, can positively impact subsequent memory performance and reduce perceived exertion during a moderate-intensity run in active males. PMID:26225993

Increasing Physical Activity and Participation in People With Multiple Sclerosis: A Review.

PubMed

Backus, Deborah

2016-09-01

Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system (CNS) affecting >2.5 million people worldwide. Damage to neurons in the CNS causes various sensorimotor and cognitive symptoms, such as fatigue, pain, spasticity, memory deficits, and impairment of mobility. Until the late 1990s, it was believed that symptoms of MS would be worsened with physical exertion and people with MS were encouraged to limit physical activity and exertion. Not only has emerging evidence suggested that physical activity, including exercise, is safe for people with MS, there is also evidence that at least some of the disability that occurs after MS is due to secondary deconditioning from the sedentary lifestyle adopted because of the symptoms of MS, not just CNS damage alone. Therefore, not only is physical activity safe, it is also required for maintaining function and health in people with MS. The purpose of this article is to review the unique physical and social barriers to physical activity in people with MS, including those with moderate to severe disability who use a wheelchair or scooter for mobility. We will discuss how existing guidelines for physical activity may not meet the needs of people with MS and present evidence-based considerations for promoting physical activity in people with MS. Ultimately, the goal is to overcome the barriers to physical activity and improve health, participation, and quality of life in people with MS. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Non-linear wave-particle interactions and fast ion loss induced by multiple Alfvén eigenmodes in the DIII-D tokamak

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Xi; Kramer, Gerrit J.; Heidbrink, William W.

2014-05-21

A new non-linear feature has been observed in fast-ion loss from tokamak plasmas in the form of oscillations at the sum, difference and second harmonic frequencies of two independent Alfvén eigenmodes (AEs). Full orbit calculations and analytic theory indicate this non-linearity is due to coupling of fast-ion orbital response as it passes through each AE — a change in wave-particle phase k • r by one mode alters the force exerted by the next. Furthermore, the loss measurement is of barely confined, non-resonant particles, while similar non-linear interactions can occur between well-confined particles and multiple AEs leading to enhanced fast-ionmore » transport.« less

On the heating mechanism of magnetic flux loops in the solar atmosphere

NASA Technical Reports Server (NTRS)

Song, M. T.; Wu, S. T.

1984-01-01

An investigation is conducted of physical heating mechanisms due to the ponderomotive forces exerted by turbulent waves along the solar atmosphere's curved magnetic flux loops. Results indicate that the temperature difference between the inside and outside of the flux loop can be classified into three parts, two of which represent the cooling or heating effect exerted by the ponderomotive force, while the third is the heating effect due to turbulent energy conversion from the localized plasma. This heating mechanism is used to illustrate solar atmospheric heating by means of an example that leads to the formulation of plages.

["Entero-insular axis" and regulation of blood sugar and insulin levels following oral glucose loading].

PubMed

Kuznetsov, B G

1978-11-01

The mineral water Essentuki 17 administered per so with glucose exerted a modifying effect on the regulation of glycaemia and insulinaemia in intact rats. This effect undergoes a few phases of changing and disappears by the 30th day. Under conditions of this adaptation, the glycaemia regulation is somewhat worsening. After i.v. administration of glucose during this period the regulation of glycaemia and insulinaemia remains unaltered. This suggests that the mineral water exerts its biological effect, mainly, on the entero-insular axis system (Unger and Eisentraut, 1969) and that the modifying effect is due not to a concrete complex of the mineral water electrolytes but rather to the unspecific factor of "perturbation" in the enteral medium.

(Why) do victims become perpetrators? Intergenerational transmission of parental violence in a representative German sample.

PubMed

Hellmann, Deborah F; Stiller, Anja; Glaubitz, Christoffer; Kliem, Sören

2018-03-01

Child maltreatment can severely impair children's emotional and physical well-being as well as their individual development across the life span. In 2011, the Criminological Research Institute of Lower Saxony (Germany), conducted a nationally representative victim survey on diverse forms of victimizations (N = 11,428). Among other things, experienced and exerted parental violence as well as participants' knowledge regarding the abolition of the parental right of corporal punishment were assessed. Apart from providing current estimates of the prevalence of experienced and exerted parental violence in Germany, we identified specific risk markers for the intergenerational transmission of parental violence. In summary, 52.6% of the participants reported experiences of at least one incident of at least minor parental violence until the age of 16 years, and 22.9% had exerted at least once at least one act of minor violence against their own children. Nonparametric conditional inference tree analyses revealed experienced parental violence as the most important risk marker for exerting parental violence. Furthermore, the number of children currently cared for, parental age, and origin as well as knowledge about the current legal situation regarding corporal punishment were significantly associated with exerting parental violence. For individuals without a history of parental violence, lack of experienced parental warmth and an age between 33 and 40 years increased the risk of exerting parental violence. The results are discussed in terms of their implications for designing effective prevention and intervention strategies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Protective effects of osthole, a natural derivative of coumarin, against intestinal ischemia-reperfusion injury in mice.

PubMed

Dong, Wenpeng; Zhang, Zhen; Liu, Zhengjun; Liu, Hao; Wang, Xianyue; Bi, Shenghui; Wang, Xiaowu; Ma, Tao; Zhang, Weida

2013-06-01

Intestinal ischemia/reperfusion (I/R) injury is considered to be associated with high morbidity and mortality rates. Osthole, a natural derivative of coumarin, has been shown to exert a variety of pharmacological and therapeutic effects under physiological and pathological conditions. In the present study, to investigate the protective effects of osthole against intestinal I/R injury, various doses of osthole (5, 10, 25 and 50 mg/kg) were pre-administered to mice subjected to intestinal I/R injury. A dose-dependent increase in the survival rate was observed in the osthole-treated mice. Pre-treatment with osthole (50 mg/kg) attenuated the destruction of epithelial cells within the villi induced by intestinal I/R injury, and suppressed oxidative stress, neutrophil infiltration and modulated nitric oxide (NO) levels. Moreover, the increased IκBα phosphorylation and nuclear factor (NF)-κB nuclear translocation induced by I/R injury were significantly decreased following pre-treatment with osthole. Taken together, our data demonstrate that osthole exerts protective effects against intestinal I/R injury in mice by suppressing oxidative stress, neutrophil infiltration and NO levels, partly through the inhibition of NF-κB nuclear translocation. Hence, the findings of the present study provide insight into the mechanisms through which osthole exerts its protective effects against intestinal I/R injury.

Psychological stress exerts an adjuvant effect on skin dendritic cell functions in vivo.

PubMed

Saint-Mezard, Pierre; Chavagnac, Cyril; Bosset, Sophie; Ionescu, Marius; Peyron, Eric; Kaiserlian, Dominique; Nicolas, Jean-Francois; Bérard, Frédéric

2003-10-15

Psychological stress affects the pathophysiology of infectious, inflammatory, and autoimmune diseases. However, the mechanisms by which stress could modulate immune responses in vivo are poorly understood. In this study, we report that application of a psychological stress before immunization exerts an adjuvant effect on dendritic cell (DC), resulting in increased primary and memory Ag-specific T cell immune responses. Acute stress dramatically enhanced the skin delayed-type hypersensitivity reaction to haptens, which is mediated by CD8(+) CTLs. This effect was due to increased migration of skin DCs, resulting in augmented CD8(+) T cell priming in draining lymph nodes and enhanced recruitment of CD8(+) T cell effectors in the skin upon challenge. This adjuvant effect of stress was mediated by norepinephrine (NE), but not corticosteroids, as demonstrated by normalization of the skin delayed-type hypersensitivity reaction and DC migratory properties following selective depletion of NE. These results suggest that release of NE by sympathetic nerve termini during a psychological stress exerts an adjuvant effect on DC by promoting enhanced migration to lymph nodes, resulting in increased Ag-specific T cell responses. Our findings may open new ways in the treatment of inflammatory diseases, e.g., psoriasis, allergic contact dermatitis, and atopic dermatitis.

Curcumin Attenuates Amyloid-β Aggregate Toxicity and Modulates Amyloid-β Aggregation Pathway.

PubMed

Thapa, Arjun; Jett, Stephen D; Chi, Eva Y

2016-01-20

The abnormal misfolding and aggregation of amyloid-β (Aβ) peptides into β-sheet enriched insoluble deposits initiates a cascade of events leading to pathological processes and culminating in cognitive decline in Alzheimer's disease (AD). In particular, soluble oligomeric/prefibrillar Aβ have been shown to be potent neurotoxins. The naturally occurring polyphenol curcumin has been shown to exert a neuroprotective effect against age-related neurodegenerative diseases such as AD. However, its protective mechanism remains unclear. In this study, we investigated the effects of curcumin on the aggregation of Aβ40 as well as Aβ40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit Aβ fibril formation, but rather enriches the population of "off-pathway" soluble oligomers and prefibrillar aggregates that were nontoxic. Curcumin also exerted a nonspecific neuroprotective effect, reducing toxicities induced by a range of Aβ conformers, including monomeric, oligomeric, prefibrillar, and fibrillar Aβ. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by Aβ aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against Aβ induced toxicity through at least two concerted pathways, modifying the Aβ aggregation pathway toward the formation of nontoxic aggregates and ameliorating Aβ-induced toxicity possibly through a nonspecific pathway.

Mangiferin inhibits hippocampal NLRP3 inflammasome and exerts antidepressant effects in a chronic mild stress mice model.

PubMed

Cao, Changfu; Su, Meiqing; Zhou, Feng

2017-08-01

A growing body of evidence suggests that inflammation may contribute toward the development of major depressive disorder. Mangiferin, a glucosylxanthone from Mangifera indica, exerts a number of biological actions, including anti-inflammatory effects. Although mangiferin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study investigated the effects of mangiferin on behavioral changes and inflammatory responses induced by chronic mild stress (CMS) in mice. We found that treatment with mangiferin for 3 weeks significantly increased the body weight of mice and ameliorated CMS-induced behavioral abnormalities by increasing sucrose consumption, improving locomotor activities, and decreasing the immobility time in the forced-swimming test and tail-suspension test. It also suppressed increased serum corticosterone levels in CMS mice. In response to CMS induction, the NLR family, pyrin domain containing 3 (NLRP3) inflammasome was activated and interleukin (IL)-1β and IL-18 levels were increased in the mouse hippocampus. Mangiferin treatment downregulated the expression of NLRP3, the adaptor protein ASC, and caspase-1, which subsequently reduced the production of IL-1β and IL-18 in CMS mice. In sum, our results indicate that mangiferin exerts antidepressant-like effects in CMS model, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression.

Mega-dose vitamin C attenuated lung inflammation in mouse asthma model.

PubMed

Jeong, Young-Joo; Kim, Jin-Hee; Kang, Jae Seung; Lee, Wang Jae; Hwang, Young-Il

2010-12-01

Asthma is a Th2-dependent disease mediated by IgE and Th2 cytokines, and asthmatic patients suffer from oxidative stresses from abnormal airway inflammation. Vitamin C is a micro-nutrient functioning as an antioxidant. When administered at a mega-dose, vitamin C has been reported to shift immune responses toward Th1. Thus, we tried to determine whether vitamin C exerted beneficial effects in asthma animal model. Asthma was induced in mice by sensitizing and challenging with ovalbumin. At the time of challenge, 3~5 mg of vitamin C was administered and the effects were evaluated. Vitamin C did not modulate Th1/Th2 balance in asthma model. However, it decreased airway hyperreactivity to methacholine, decreased inflammatory cell numbers in brochoalveolar lavage fluid, and moderate reduction of perivascular and peribronchiolar inflammatory cell infiltration. These results suggest that vitamin C administered at the time of antigen challenge exerted anti-inflammatory effects. Further studies based on chronic asthma model are needed to evaluate a long-term effect of vitamin C in asthma. In conclusion, even though vitamin C did not show any Th1/Th2 shifting effects in this experiment, it still exerted moderate anti-inflammatory effects. Considering other beneficial effects and inexpensiveness of vitamin C, mega-dose usage of vitamin C could be a potential supplementary modality for the management of asthma.

Additive antithrombotic effect of ASP6537, a selective cyclooxygenase (COX)-1 inhibitor, in combination with clopidogrel in guinea pigs.

PubMed

Sakata, Chinatsu; Suzuki, Ken-Ichi; Morita, Yoshiaki; Kawasaki, Tomihisa

2017-03-05

Clopidogrel (Plavix ® , Sanofi-Aventis), the adenosine diphosphate P2Y 12 receptor antagonist, is reported to be effective in the prevention of cardiovascular events and is often used in combination with aspirin, particularly in high-risk patients. ASP6537 is a reversible cyclooxygenase (COX)-1 inhibitor that is under investigation as an anti-platelet agent. First, we investigated the reversibility of the antiplatelet effect of ASP6537 and its interaction with ibuprofen to compare the usability of ASP6537 with that of aspirin. We then evaluated the antithrombotic effect of ASP6537 in combination with clopidogrel using a FeCl 3 -induced thrombosis model in guinea pigs. ASP6537 exerted reversible antiplatelet activity, and no pharmacodynamic interaction with ibuprofen was noted. When administered as monotherapy, ASP6537 exerted a significant antithrombotic effect at ≥3mg/kg, while aspirin inhibited thrombosis at 100mg/kg. ASP6537 exerted significant additive effects in combination with clopidogrel, and the minimum antithrombotic dose was reduced by concomitant administration of clopidogrel. Our study showed that ASP6537 did not interact with ibuprofen and has clear additive effects in combination with clopidogrel. ASP6537 may therefore represent a promising antiplatelet agent for use in clinical settings in combination with clopidogrel. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of some non-conventional herbal medications (sulforaphane, tanshinone IIA, and tetramethylpyrazine) in inducing neuroprotection in comparison with interleukin-10 after spinal cord injury: A meta-analysis

PubMed Central

Koushki, Davood; Latifi, Sahar; Norouzi Javidan, Abbas; Matin, Marzieh

2015-01-01

Context Inflammation after spinal cord injury (SCI) may be responsible for further neural damages and therefore inhibition of inflammatory processes may exert a neuroprotection effect. Objectives To assess the efficacy of some non-conventional herbal medications including sulforaphane, tanshinone IIA, and tetramethylpyrazine in reducing inflammation and compare them with a known effective anti-inflammatory agent (interleukin-10 (IL-10)). Methods We searched relevant articles in Ovid database, Medline (PubMed) EMBASE, Google Scholar, Cochrane, and Scopus up to June 2013. The efficacy of each treatment and study powers were compared using random effects model of meta-analysis. To our knowledge, no conflict of interest exists. Results Eighteen articles entered into the study. The meta-analysis revealed that exogenous IL-10 was more effective in comparison with the mentioned herbal extracts. The proposed pathways for each medication's effect on reducing the inflammation process are complex and many overlaps may exist. Conclusion IL-10 has a strong effect in the induction of neuroprotection and neurorecovery after SCI by multiple pathways. Tetramethylpyrazine has an acceptable influence in reducing inflammation through the up-regulation of IL-10. Outcomes of sulforaphane and tanshinone IIA administration are acceptable but still weaker than IL-10. PMID:24969510

Efficacy of some non-conventional herbal medications (sulforaphane, tanshinone IIA, and tetramethylpyrazine) in inducing neuroprotection in comparison with interleukin-10 after spinal cord injury: A meta-analysis.

PubMed

Koushki, Davood; Latifi, Sahar; Norouzi Javidan, Abbas; Matin, Marzieh

2015-01-01

Inflammation after spinal cord injury (SCI) may be responsible for further neural damages and therefore inhibition of inflammatory processes may exert a neuroprotection effect. To assess the efficacy of some non-conventional herbal medications including sulforaphane, tanshinone IIA, and tetramethylpyrazine in reducing inflammation and compare them with a known effective anti-inflammatory agent (interleukin-10 (IL-10)). We searched relevant articles in Ovid database, Medline (PubMed) EMBASE, Google Scholar, Cochrane, and Scopus up to June 2013. The efficacy of each treatment and study powers were compared using random effects model of meta-analysis. To our knowledge, no conflict of interest exists. Eighteen articles entered into the study. The meta-analysis revealed that exogenous IL-10 was more effective in comparison with the mentioned herbal extracts. The proposed pathways for each medication's effect on reducing the inflammation process are complex and many overlaps may exist. IL-10 has a strong effect in the induction of neuroprotection and neurorecovery after SCI by multiple pathways. Tetramethylpyrazine has an acceptable influence in reducing inflammation through the up-regulation of IL-10. Outcomes of sulforaphane and tanshinone IIA administration are acceptable but still weaker than IL-10.

Bottom-up vs. top-down effects on terrestrial insect herbivores: a meta-analysis.

PubMed

Vidal, Mayra C; Murphy, Shannon M

2018-01-01

Primary consumers are under strong selection from resource ('bottom-up') and consumer ('top-down') controls, but the relative importance of these selective forces is unknown. We performed a meta-analysis to compare the strength of top-down and bottom-up forces on consumer fitness, considering multiple predictors that can modulate these effects: diet breadth, feeding guild, habitat/environment, type of bottom-up effects, type of top-down effects and how consumer fitness effects are measured. We focused our analyses on the most diverse group of primary consumers, herbivorous insects, and found that in general top-down forces were stronger than bottom-up forces. Notably, chewing, sucking and gall-making herbivores were more affected by top-down than bottom-up forces, top-down forces were stronger than bottom-up in both natural and controlled (cultivated) environments, and parasitoids and predators had equally strong top-down effects on insect herbivores. Future studies should broaden the scope of focal consumers, particularly in understudied terrestrial systems, guilds, taxonomic groups and top-down controls (e.g. pathogens), and test for more complex indirect community interactions. Our results demonstrate the surprising strength of forces exerted by natural enemies on herbivorous insects, and thus the necessity of using a tri-trophic approach when studying insect-plant interactions. © 2017 John Wiley & Sons Ltd/CNRS.

Role of L-arginine in the biological effects of blue light

NASA Astrophysics Data System (ADS)

Makela, Anu M.

2005-11-01

Arginine, a semi-essential amino acid, and metabolites of arginine exert multiple biological effects. It has been known that arginine causes the release of various hormones such as insulin, glucagon, growth hormone, prolactin, and adrenal catecholamines. Arginine infusion also produces vasodilation, and in the kidney increased plasma flow accompanied by increases in glomerular filtration rate (GFR). Recent studies have showed that blue and red light irradiation in vitro and in vivo can increase production of nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS). These then can modulate the production and secretion of several cytokines and other mediators and play an important role as regulatory mediators in signaling processes which can then modulate the production, mobilization and homing of stem cells. It is proposed that some of the therapeutic effects of light can be considered to be due to the changes in the metabolism of L-arginine. The regulation of L-arginine turnover by the use of light at blue wavelengths between 400nm and 510nm can be the explanation for some of the observed effects of blue light: lowering of blood pressure, pain killing effect, regulating insulin production, anti-inflammatory action, and possible effects on the release and homing of stem cells.

NLR-Dependent Regulation of Inflammation in Multiple Sclerosis

PubMed Central

Gharagozloo, Marjan; Gris, Katsiaryna V.; Mahvelati, Tara; Amrani, Abdelaziz; Lukens, John R.; Gris, Denis

2018-01-01

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) associated with inappropriate activation of lymphocytes, hyperinflammatory responses, demyelination, and neuronal damage. In the past decade, a number of biological immunomodulators have been developed that suppress the peripheral immune responses and slow down the progression of the disease. However, once the inflammation of the CNS has commenced, it can cause serious permanent neuronal damage. Therefore, there is a need for developing novel therapeutic approaches that control and regulate inflammatory responses within the CNS. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are intracellular regulators of inflammation expressed by many cell types within the CNS. They redirect multiple signaling pathways initiated by pathogens and molecules released by injured tissues. NLR family members include positive regulators of inflammation, such as NLRP3 and NLRC4 and anti-inflammatory NLRs, such as NLRX1 and NLRP12. They exert immunomodulatory effect at the level of peripheral immune responses, including antigen recognition and lymphocyte activation and differentiation. Also, NLRs regulate tissue inflammatory responses. Understanding the molecular mechanisms that are placed at the crossroad of innate and adaptive immune responses, such as NLR-dependent pathways, could lead to the discovery of new therapeutic targets. In this review, we provide a summary of the role of NLRs in the pathogenesis of MS. We also summarize how anti-inflammatory NLRs regulate the immune response within the CNS. Finally, we speculate the therapeutic potential of targeting NLRs in MS. PMID:29403486

Early Socioeconomic Adversity and Young Adult Physical Illness: The Role of Body Mass Index and Depressive Symptoms

PubMed Central

Wickrama, K. A. S.; Kwon, Josephine A.; Oshri, Assaf; Lee, Tae Kyoung

2014-01-01

Purpose The present study investigated the psycho-physiological inter and intra-individual processes that mediate the linkage between childhood/adolescent socioeconomic adversities and adult health outcomes. Specifically, the proposed model examined the roles of youth depressive symptoms and BMI trajectories as mediators that explain the link between early adversity and young adults’ general health and physical illnesses after controlling for gender, race/ethnicity, and earlier general health reports. Methods Using a nationally representative sample of 12,424 from National Longitudinal Study of Adolescent Health (Add Health), this study used growth curve modeling to consider both the severity (initial level) as well as the change over time (deterioration or elevation) as psycho-physiological mediators, thereby acknowledging multiple facets of depressive symptoms and BMI trajectories as psych-physiological mediators of early adversity to adult health. Results Results provide evidence for (a) the influence of early childhood and early adolescent cumulative socioeconomic adversity on both the initial levels and changes over time of depressive symptoms and BMI and (b) the independent influences depressive symptoms and BMI trajectories on the general health and the physical illnesses of young adults Conclusions These findings contribute valuable knowledge to existing research by elucidating how early adversity exerts an enduring long-term influence on physical health problems in young adulthood; further, this information suggests effective intervention and prevention programs should incorporate multiple facets (severity and change over time) of multiple mechanisms (psychological and physiological). PMID:24856408

Predicting right-wing authoritarianism via personality and dangerous world beliefs: direct, indirect, and interactive effects.

PubMed

Dallago, Francesca; Mirisola, Alberto; Roccato, Michele

2012-01-01

In an Italian sample (N = 483, 78.23% women, mean age = 27.61 years old), we used structural equation modeling with latent variables and interactions to analyze the direct, indirect, and interactive effects exerted on right-wing authoritarianism by the Big Five factors of personality and by dangerous world beliefs. Openness, Neuroticism, and Conscientiousness exerted direct effects on right-wing authoritarianism; the first two relationships were partially mediated by dangerous world beliefs. Most importantly, the relationship between dangerous world beliefs and right-wing authoritarianism was moderated by Openness: dangerous world beliefs significantly influenced right-wing authoritarianism solely for participants high in Openness. Limitations and possible developments of this research are discussed.

Reasons for living, social support, and Afrocentric worldview: assessing buffering factors related to Black Americans' suicidal behavior.

PubMed

Wang, Mei-Chuan; Joel Wong, Y; Tran, Kimberly K; Nyutu, Pius N; Spears, Angela

2013-01-01

This study utilized an ecological framework to explore the role of 4 culturally relevant protective factors-reasons for living, Afrocentric worldview, family support, and friend support-in protecting Black American college students from suicidal behavior. Participants were 289 Black American college students. We hypothesized that these 4 culturally relevant factors would exert indirect protective effects on suicidal behavior through their association with reduced depressive symptoms. Results indicated that reasons for living, perceived supportive behaviors from family, and Afrocentric worldview exerted indirect protective effects on suicidal behaviors through their negative associations with depressive symptoms. The mediation effect from friend support to depression and suicidal behavior was not significant.

Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology.

PubMed

Salamone, John D; Yohn, Samantha E; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

2016-05-01

Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson's disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision-making are highly translatable to humans, and an emerging body of evidence indicates that alterations in effort-based decision-making are evident in several psychiatric and neurological disorders. People with major depression, schizophrenia, and Parkinson's disease show evidence of decision-making biases towards a lower exertion of effort. Translational studies linking research with animal models, human volunteers, and clinical populations are greatly expanding our knowledge about the neural basis of effort-related motivational dysfunction, and it is hoped that this research will ultimately lead to improved treatment for motivational and psychomotor symptoms in psychiatry and neurology. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Estrogens facilitate memory processing through membrane mediated mechanisms and alterations in spine density

PubMed Central

Luine, Victoria N.; Frankfurt, Maya

2012-01-01

Estrogens exert sustained, genomically mediated effects on memory throughout the female life cycle, but here we review new studies documenting rapid effects of estradiol on memory, which are exerted through membrane-mediated mechanisms. Use of recognition memory tasks in rats, shows that estrogens enhance memory consolidation within one hour. 17α-estradiol is more potent than 17β-estradiol, and the dose response relationship between estrogens and memory is an inverted U shape. Use of specific estrogen receptor (ER) agonists suggests mediation by an ERβ-like membrane receptor. Enhanced memory is associated with increased spine density and altered noradrenergic activity in the medial prefrontal cortex and hippocampus within 30 min. of administration. The environmental chemical, bisphenol-A, rapidly antagonizes enhancements in memory in both sexes possibly through actions on spines. Thus, estradiol and related compounds exert rapid alterations in cognition through non-genomic mechanisms, a finding which may provide a basis for better understanding and treating memory impairments. PMID:22981654

Arthropod repellency, especially tick (Ixodes ricinus), exerted by extract from Artemisia abrotanum and essential oil from flowers of Dianthus caryophyllum.

PubMed

Tunón, H; Thorsell, W; Mikiver, A; Malander, I

2006-06-01

A toluene extract of southernwood (Artemisia abrotanum) and the essential oil from flowers of carnation (Dianthus caryophyllum ) exerted pronounced a repellent effect both against ticks (nymphs of Ixodes ricinus) and yellow fever mosquitoes (Aedes aegypti). The most potent repellents found were coumarin and thujyl alcohol from A. abrotanum and phenylethanol from D. caryophyllum where coumarin and thujyl alcohol were also detected.

The impact of clinical, psychological, behavioral, social, and environmental factors on self-perceived symptom severity in a male cohort with intermittent claudication.

PubMed

Sharath, Sherene E; Kougias, Panos; Pisimisis, George; Barshes, Neal R

2016-05-01

To understand the relationship between self-perceived severity of intermittent claudication and various associated nonclinical factors, we examined how correlates in domains of physical activity (ie, clinical, psychological, behavioral, social, and environmental factors) relate to exertional limb symptoms. A survey was administered to individuals with intermittent claudication during their initial outpatient assessment. The subjects' self-reported exertional limb symptom severity and classic-versus-atypical claudication classification was based on the Walking Impairment Questionnaire (WIQ) and San Diego Claudication Questionnaire (SDCQ), respectively. We evaluated psychosocial and environmental factors, osteoarthritis symptoms, health, behaviors, and beliefs. Logistic and linear regressions identified factors with a strong independent association with total WIQ scores and the SDCQs. A cohort of 102 subjects (99.0% male) was enrolled in the study. The median age was 65 years with a median ankle-brachial index of 0.69. Forty-three subjects (43%) had "typical" claudication per SDCQs. Individuals with atypical claudication were more likely to report higher Aberdeen Clinical Back Pain Questionnaire scores (odds ratio, 1.04; P = .04) and no depressive symptoms (odds ratio, 8.30; P = .03). Exertional limb symptom severity among the entire cohort was significantly associated with increasing osteoarthritis symptoms (P <.001), age (P = .02), a reserved personality (P = .008), and the belief that an exercise regimen would not improve symptoms (P = .005), self-perceived levels of boredom (P = .002), and the belief that exercise (P = .002) was the best way to improve symptoms were associated with decreased symptom severity. When restricted to those with atypical pain, significant factors associated with increasing exertional symptom severity included age greater than 60 years (P = .005), osteoarthritis (P = .02), alcohol use (P = .01), belief that exercise would not improve walking (P = .03), and difficulty walking around the neighborhood (P = .02). When restricted to those with classic claudication, significant factors associated with increasing exertional limb symptom severity included frequent pain or aching in the calves while walking or sitting (P = .03 [walking]; P = .01 [sitting]) and occasional morning joint stiffness (P = .007). Exertional limb symptom severity was also associated with high limitations at home (P = .003) and a belief that exercise would not improve walking (P = .005) among those with classic claudication. Symptom severity and type of pain are associated with a number of nonclinical factors. A multidomain approach, as indicated by the models above, would benefit the continuum of care for intermittent claudication, where management is integrated and coordinated among multiple lines of care. Published by Elsevier Inc.

Post-exertion neurocognitive test failure among student-athletes following concussion.

PubMed

McGrath, Neal; Dinn, Wayne M; Collins, Michael W; Lovell, Mark R; Elbin, R J; Kontos, Anthony P

2013-01-01

The purpose of the present study was to examine post-exertion (PE) neurocognitive performance among student-athletes following concussion who were asymptomatic and returned to baseline normal neurocognitive test levels at rest. This study examined the neurocognitive performance of a sub-set of student-athletes who 'failed' to perform at baseline levels of neurocognitive function, i.e. exhibited downward reliable change index (RCI) alterations following a moderate exertional protocol during recovery from concussion. A retrospective records review was carried out of Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) and neuropsychological consultation data among athletes with sports-related concussion from a network of 22 schools and one junior hockey programme. Fifty-four student-athletes met inclusion criteria and participated in the study. A total of 27.7% of concussed student-athletes who were symptom-free and returned to baseline on ImPACT at rest (i.e. no longer demonstrated performance deficits on neurocognitive tests) exhibited cognitive decline following moderate physical exertion. The PE cognitive changes were not simply general performance effects, but significant changes in memory ability in the presence of intact processing speed functions. The PE-Pass and PE-Fail groups did not, however, differ on post-concussive symptoms or concussion history. Clinicians' return-to-play evaluation protocols should include post-exertional computerized neurocognitive testing.

Individual and Neighborhood Stressors, Air Pollution and Cardiovascular Disease.

PubMed

Hazlehurst, Marnie F; Nurius, Paula S; Hajat, Anjum

2018-03-08

Psychosocial and environmental stress exposures across the life course have been shown to be relevant in the development of cardiovascular disease (CVD). Assessing more than one stressor from different domains (e.g., individual and neighborhood) and across the life course moves us towards a more integrated picture of how stress affects health and well-being. Furthermore, these individual and neighborhood psychosocial stressors act on biologic pathways, including immune function and inflammatory response, which are also impacted by ubiquitous environmental exposures such as air pollution. The objective of this study is to evaluate the interaction between psychosocial stressors, at both the individual and neighborhood level, and air pollution on CVD. This study used data from the 2009-2011 Behavioral Risk Factor Surveillance System (BRFSS) from Washington State. Adverse childhood experiences (ACEs) measured at the individual level, and neighborhood deprivation index (NDI) measured at the zip code level, were the psychosocial stressors of interest. Exposures to three air pollutants-particulate matter (both PM 2.5 and PM 10 ) and nitrogen dioxide (NO₂)-were also calculated at the zip code level. Outcome measures included several self-reported CVD-related health conditions. Both multiplicative and additive interaction quantified using the relative excess risk due to interaction (RERI), were evaluated. This study included 32,151 participants in 502 unique zip codes. Multiplicative and positive additive interactions were observed between ACEs and PM 10 for diabetes, in models adjusted for NDI. The prevalence of diabetes was 1.58 (95% CI: 1.40, 1.79) times higher among those with both high ACEs and high PM 10 compared to those with low ACEs and low PM 10 ( p -value = 0.04 for interaction on the multiplicative scale). Interaction was also observed between neighborhood-level stressors (NDI) and air pollution (NO₂) for the stroke and diabetes outcomes on both multiplicative and additive scales. Modest interaction was observed between NDI and air pollution, supporting prior literature on the importance of neighborhood-level stressors in cardiovascular health and reinforcing the importance of NDI on air pollution health effects. ACEs may exert health effects through selection into disadvantaged neighborhoods and more work is needed to understand the accumulation of risk in multiple domains across the life course.

Higher motivation - greater control? The effect of arousal on judgement.

PubMed

Riemer, Hila; Viswanathan, Madhu

2013-01-01

This research examines control over the effect of arousal, a dimension of affect, on judgement. Past research shows that high processing motivation enhances control over the effects of affect on judgement. Isolating and studying arousal as opposed to valence, the other dimension of affect, and its effect on judgement, we identify boundary conditions for past findings. Drawing from the literature on processes by which arousal influences judgement, we demonstrate that the role of motivation is contingent upon the type of judgement task (i.e., memory- versus stimulus-based judgement). In stimulus-based judgement, individuals exert greater control over the effect of arousal on judgement under low compared to high motivation. In contrast, in memory-based judgement individuals exert greater control over the effect of arousal under high compared to low motivation. Theoretical implications and avenues for future research are discussed.

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer in vitro.

PubMed

Yoshino, Hironori; Iwabuchi, Miyu; Kazama, Yuka; Furukawa, Maho; Kashiwakura, Ikuo

2018-04-01

Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy. However, it is unclear whether ionizing radiation affects the cytotoxicity of RLR agonists against cancer cells. Therefore, in the present study the effects of cotreatment with ionizing radiation and RLR agonists on cytotoxicity against human non-small cell lung cancer cells A549 and H1299 was investigated. Treatment with RLR agonist poly(I:C)/LyoVec™ [poly(I:C)] exerted cytotoxic effects against human non-small cell lung cancer. The cytotoxic effects of poly(I:C) were enhanced by cotreatment with ionizing radiation, and poly(I:C) pretreatment resulted in the radiosensitization of non-small cell lung cancer. Furthermore, cotreatment of A549 and H1299 cells with poly(I:C) and ionizing radiation effectively induced apoptosis in a caspase-dependent manner compared with treatment with poly(I:C) or ionizing radiation alone. These results indicate that RLR agonists and ionizing radiation cotreatment effectively exert cytotoxic effects against human non-small cell lung cancer through caspase-mediated apoptosis.

Infusions of allopregnanolone into the hippocampus and amygdala, but not into the nucleus accumbens and medial prefrontal cortex, produce antidepressant effects on the learned helplessness rats.

PubMed

Shirayama, Yukihiko; Muneoka, Katsumasa; Fukumoto, Makoto; Tadokoro, Shigenori; Fukami, Goro; Hashimoto, Kenji; Iyo, Masaomi

2011-10-01

Patients with depression showed a decrease in plasma and cerebrospinal fluid allopregnanolone (ALLO). But antidepressants increased the contents of ALLO in the rat brain. We examined the antidepressant-like effects of infusion of ALLO into the cerebral ventricle, hippocampus, amygdala, nucleus accumbens, or prefrontal cortex of learned helplessness (LH) rats (an animal model of depression). Of these regions, infusions of ALLO into the cerebral ventricle, the CA3 region of hippocampus, or the central region of amygdala exerted antidepressant-like effects. Infusion of ALLO into the hippocampal CA3 region or the central amygdala did not produce memory deficits or locomotor activation in the passive avoidance and open field tests. It is well documented that ALLO exerts its effects through GABA receptors. Therefore, we examined the antagonistic effects of flumazenil (a GABA receptor antagonist) on the antidepressant-like effects of ALLO. Coinfusion of flumazenil with ALLO into the hippocampal CA3 region, but not into the central amygdala, blocked the antidepressant-like effects of ALLO. However, coinfusion of (+)MK801 (an NMDA receptor antagonist), but not cycloheximide (a protein synthesis inhibitor), blocked the antidepressant-like effects of ALLO in the central amygdala. These results suggest that ALLO exerts antidepressant-like effects in the CA3 region of hippocampus through the GABA system and in the central region of amygdala, dependently on the activation of the glutamatergic mechanisms. Copyright © 2010 Wiley-Liss, Inc.

The Role of GABRA2 in Alcohol Dependence, Smoking and Illicit Drug Use in an Australian Population Sample

PubMed Central

Lind, Penelope A; Macgregor, Stuart; Agrawal, Arpana; Montgomery, Grant W; Heath, Andrew C; Martin, Nicholas G; Whitfield, John B

2008-01-01

Background Multiple studies have shown that genetic variation in the α-2 subunit of the GABA-A receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol's intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested for association between GABRA2 and alcohol dependence, smoking and illicit drug use within the Australian population. Methods We genotyped 11 single nucleotide polymorphisms within or flanking GABRA2 in 4597 subjects (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic pairs and 627 twins whose co-twin did not participate. Family-based association tests were conducted for binary and quantitative measures of alcohol dependence, smoking, cannabis and other illicit drug use. Results We observed evidence of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures of alcohol dependence, including symptom scores and principal component factor scores from the 9 criteria for DSM-IV alcohol dependence, in the opposite direction to that previously reported. In contrast, GABRA2 was not associated overall with dichotomous measure of alcohol dependence, nor with smoking, cannabis or illicit drug use. Conclusions The GABRA2 allelic associations found in clinical case-control studies have detectable but minor effects on DSM-defined alcohol dependence in the general community. Systematic comparisons of allelic effects on alcohol dependence in clinical cases and in the general community are required. PMID:18727688

Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

PubMed

Nabissi, Massimo; Morelli, Maria Beatrice; Offidani, Massimo; Amantini, Consuelo; Gentili, Silvia; Soriani, Alessandra; Cardinali, Claudio; Leoni, Pietro; Santoni, Giorgio

2016-11-22

Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy. In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines. We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis. Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein. Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ. Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration. In summary, these results proved that this combination exerts strong anti-myeloma activities.

Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in experimental autoimmune encephalomyelitis.

PubMed

Medina-Fernández, Francisco J; Luque, Evelio; Aguilar-Luque, Macarena; Agüera, Eduardo; Feijóo, Montserrat; García-Maceira, Fe I; Escribano, Begoña M; Pascual-Leone, Álvaro; Drucker-Colín, René; Túnez, Isaac

2017-01-15

Experimental autoimmune encephalomyelitis (EAE) is considered a valid experimental model for multiple sclerosis, a chronic neuroinflammatory condition of the central nervous system. Additionally, some evidence has shown that some microbial products such as the bacterial lipopolysaccharide could lead to the activation of reactive immune cells, triggering neuroinflammation. Several studies have found that transcranial magnetic stimulation (TMS) may exert a neuroprotective effect. Therefore, we aimed to assess the effect of TMS on the neuroinflammation occurring in EAE. A total of 44 male Dark Agouti rats were used. EAE induction was performed administering subcutaneously at the dorsal base of the tail a single dose of myelin oligodendrocyte glycoprotein. Clinical evaluation of motor symptoms was performed. Brain and spinal cord were collected and analyzed for nitric oxide, bacterial lipopolysaccharide and lipopolysaccharide-binding protein. We also carried out a histologic exam, which included an astrocyte immunostaining and Nissl staining for the assessment of brain cell density and pyknotic nuclei. TMS effectively ameliorated motor impairment secondary to EAE. This form of magnetic field was capable of decreasing the proliferation of astrocytes as a response to the autoimmune attack, reducing the content of nitric oxide, bacterial lipopolysaccharide and lipopolysaccharide-binding protein in central nervous system. Moreover, in treated animals, brain cell density was improved and the number of pyknotic nuclei was decreased. Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in EAE. These results suggest that TMS could be a promising treatment for neuroinflammatory conditions such as multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Model based population PK-PD analysis of furosemide for BP lowering effect: A comparative study in primary and secondary hypertension.

PubMed

Shukla, Mahendra; Ibrahim, Moustafa M A; Jain, Moon; Jaiswal, Swati; Sharma, Abhisheak; Hanif, Kashif; Lal, Jawahar

2017-11-15

Though numerous reports have demonstrated multiple mechanisms by which furosemide can exert its anti-hypertensive response. However, lack of studies describing PK-PD relationship for furosemide featuring its anti-hypertensive property has limited its usage as a blood pressure (BP) lowering agent. Serum concentrations and mean arterial BP were monitored following 40 and 80mgkg -1 multiple oral dose of furosemide in spontaneously hypertensive rats (SHR) and DOCA-salt induced hypertensive (DOCA-salt) rats. A simultaneous population PK-PD relationship using E max model with effect compartment was developed to compare the anti-hypertensive efficacy of furosemide in these rat models. A two-compartment PK model with Weibull-type absorption and first-order elimination best described the serum concentration-time profile of furosemide. In the present study, post dose serum concentrations of furosemide were found to be lower than the EC 50 . The EC 50 predicted in DOCA-salt rats was found to be lower (4.5-fold), whereas the tolerance development was higher than that in SHR model. The PK-PD parameter estimates, particularly lower values of EC 50 , K e and Q in DOCA-salt rats as compared to SHR, pinpointed the higher BP lowering efficacy of furosemide in volume overload induced hypertensive conditions. Insignificantly altered serum creatinine and electrolyte levels indicated a favorable side effect profile of furosemide. In conclusion, the final PK-PD model described the data well and provides detailed insights into the use of furosemide as an anti-hypertensive agent. Copyright © 2017. Published by Elsevier B.V.

Costunolide inhibits proinflammatory cytokines and iNOS in activated murine BV2 microglia.

PubMed

Rayan, Nirmala Arul; Baby, Nimmi; Pitchai, Daisy; Indraswari, Fransisca; Ling, Eng-Ang; Lu, Jia; Dheen, Thameem

2011-06-01

Costunolide, a sesquiterpene lactone present in Costus speciosus root exerts a variety of pharmacological activity but its effects on neuroinflammation have not been studied. Microglia, the resident phagocytic cells in the central nervous system respond to neuroinflammation and their overwhelming response in turn aggravate brain damage during infection, ischemia and neurodegenerative diseases. In this study, we report the effect of Costunolide on the production of proinflammatory mediators and mechanisms involved in BV2 microglial cells stimulated with LPS. Costunolide attenuated the expression of tumour necrosis factor-alpha, interleukin-1,6, inducible nitric oxide synthase, monocyte chemotactic protein 1 and cyclooxygenase 2 in activated microglia. This Costunolide-mediated inhibition was correspondent with the inhibition of NFkappaB activation. It has been further shown that Costunolide suppressed MAPK pathway activation by inducing MKP-1 production. Collectively our results suggest that Costunolide shows an ability to inhibit expression of multiple neuroinflammatory mediators and this is attributable to the compounds inhibition of NFkappaB and MAPK activation. This novel role of Costunolide upon investigation may aid in developing better therapeutic strategies for treatment of neuroinflammatory diseases.

Ethnic Pride, Traditional Family Values, and Acculturation in Early Cigarette and Alcohol Use Among Latino Adolescents

PubMed Central

Stein, Judith A.; Bentler, Peter M.

2010-01-01

A structural equations model examined the influence of three cultural variables of ethnic pride, traditional family values and acculturation, along with the mediating variables of avoidance self-efficacy and perceptions of the “benefits” of cigarette smoking, on cigarette and alcohol use in a sample of Latino middle school students in the Southwest. Girls (N = 585) and boys (N = 360) were analyzed separately. In both groups, higher ethnic pride and traditional family values exerted indirect effects on less cigarette smoking and alcohol use when mediated through greater self-efficacy and less endorsement of the “benefits” of cigarette smoking. Among the girls, greater ethnic pride also had a direct effect on less cigarette and alcohol use. Also, greater acculturation directly predicted more cigarette and alcohol use among the girls, but not among the boys. However, differences between the boys and girls were generally nonsignificant as revealed by multiple group latent variable models. These results offer implications for incorporating cultural variables into the design of culturally relevant prevention interventions that discourage cigarette and alcohol use among Latino adolescents. PMID:19415497

[Diet and gut microbiota: two sides of the same coin?

PubMed

Schiumerini, Ramona; Pasqui, Francesca; Festi, Davide

2018-01-01

Gut microbiota is a complex ecosystem, resident in the digestive tract, exerting multiple functions that can have a significant impact on the pathophysiology of the host organism. The composition and functions of this "superorganism" are influenced by many factors, and among them, the host's dietary habits seem to have a significant effect. Dietary changes in the evolution of human history and in the different stages of life of the human subjects are responsible for qualitative and functional modification of gut microbiota. At the same time, the different dietary models adopted in worldwide geographic areas take into account the inter-individual differences concerning composition and microbial function. This close relationship between diet, gut microbiota and host seems, in fact, to be responsible for the protection or predisposition to develop several metabolic, immunological, neoplastic and functional diseases. Thus, several studies have evaluated the impact of diet and lifestyle modification strategies on gut microbiota composition and functions which, in turn, seems to affect the effectiveness of such therapeutic measures. Gut microbiota manipulation strategies, as complementary to dietary modifications, represent a fascinating field of research, even if consolidated data are still lacking.

Cyclic 3',5'-adenosine monophosphate (cAMP) signaling in the anterior pituitary gland in health and disease.

PubMed

Hernández-Ramírez, Laura C; Trivellin, Giampaolo; Stratakis, Constantine A

2018-03-05

The cyclic 3',5'-adenosine monophosphate (cAMP) was the first among the so-called "second messengers" to be described. It is conserved in most organisms and functions as a signal transducer by mediating the intracellular effects of multiple hormones and neurotransmitters. In this review, we first delineate how different members of the cAMP pathway ensure its correct compartmentalization and activity, mediate the terminal intracellular effects, and allow the crosstalk with other signaling pathways. We then focus on the pituitary gland, where cAMP exerts a crucial function by controlling the responsiveness of the cells to hypothalamic hormones, neurotransmitters and peripheral factors. We discuss the most relevant physiological functions mediated by cAMP in the different pituitary cell types, and summarize the defects affecting this pathway that have been reported in the literature. We finally discuss how a deregulated cAMP pathway is involved in the pathogenesis of pituitary disorders and how it affects the response to therapy. Copyright © 2017. Published by Elsevier B.V.

Application of bee venom and its main constituent melittin for cancer treatment.

PubMed

Liu, Cui-Cui; Hao, Ding-Jun; Zhang, Qian; An, Jing; Zhao, Jing-Jing; Chen, Bo; Zhang, Ling-Ling; Yang, Hao

2016-12-01

Bee venom and its main constituent melittin (MEL) have been extensively studied in the treatment of tumors. However, the non-specific cytotoxicity and hemolytic activity have hampered the clinical application. Currently, a number of research groups have reported a series of optimization strategies, including gene therapy, recombinant immunotoxin incorporating MEL or MEL nanoparticles, targeting tumor cells to attenuate the cytotoxicity and improve its antitumor efficiency and therapeutic capabilities, which have shown very promising in overcoming some of these obstacles. In this review, we summarize the current knowledge regarding anticancer effects of bee venom and its main compound MEL on different kinds of tumor cells as well as elucidate their possible anticancer mechanisms. It could be concluded that MEL exerts multiple effects on cellular functions of cancerous cells such as proliferation, apoptosis, metastasis, angiogenesis as well as cell cycle, and the anticancer processes involve diverse signal molecules and regulatory pathways. We also highlight the recent research progress for efficient delivery of MEL peptide, thus providing new ideas and hopeful strategies for the in vivo application of MEL.

Inhibitory effect of chlorogenic acid on digestion of potato starch.

PubMed

Karim, Zida; Holmes, Melvin; Orfila, Caroline

2017-02-15

The effect of the chlorogenic acid isomer 5-O-caffeoylquinic acid (5-CQA) on digestion of potato starch by porcine pancreatic alpha amylase (PPAA) was investigated using isolated starch and cooked potato tuber as substrates. In vitro digestion was performed on five varieties of potato with varying phenolic content. Co- and pre-incubation of PPAA with 5-CQA significantly reduced PPAA activity in a dose dependent manner with an IC50 value of about 2mgmL(-1). Lineweaver-Burk plots indicated that 5-CQA exerts a mixed type inhibition as km increased and Vmax decreased. The total polyphenol content (TPC) of peeled tuber tissue ranged from 320.59 to 528.94mg 100g(-1)dry weight (DW) in raw tubers and 282.03-543.96mg 100g(-1)DW in cooked tubers. With the exception of Désirée, TPC and 5-CQA levels decreased after cooking. Principle component analysis indicated that digestibility is affected by multiple factors including phenolic, dry matter and starch content. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid

PubMed Central

Kozela, Ewa; Juknat, Ana; Vogel, Zvi

2017-01-01

The astrocytes have gained in recent decades an enormous interest as a potential target for neurotherapies, due to their essential and pleiotropic roles in brain physiology and pathology. Their precise regulation is still far from understood, although several candidate molecules/systems arise as promising targets for astrocyte-mediated neuroregulation and/or neuroprotection. The cannabinoid system and its ligands have been shown to interact and affect activities of astrocytes. Cannabidiol (CBD) is the main non-psychotomimetic cannabinoid derived from Cannabis. CBD is devoid of direct CB1 and CB2 receptor activity, but exerts a number of important effects in the brain. Here, we attempt to sum up the current findings on the effects of CBD on astrocyte activity, and in this way on central nervous system (CNS) functions, across various tested models and neuropathologies. The collected data shows that increased astrocyte activity is suppressed in the presence of CBD in models of ischemia, Alzheimer-like and Multiple-Sclerosis-like neurodegenerations, sciatic nerve injury, epilepsy, and schizophrenia. Moreover, CBD has been shown to decrease proinflammatory functions and signaling in astrocytes. PMID:28788104

Epigenetic regulation of miRNA-Cancer Stem Cells nexus by Nutraceuticals

PubMed Central

Ahmad, Aamir; Li, Yiwei; Bao, Bin; Kong, Dejuan; Sarkar, Fazlul H.

2014-01-01

Nutraceuticals, the bioactive food components represented by many naturally occurring dietary compounds, have been investigated for a few decades for their numerous beneficial effects, including their anticancer properties. The initial interest in the cancer-preventing/therapeutic ability of these agents was based on their ability to affect multiple signaling pathways that are deregulated in cancer cells. With a shift in the focus of cancer research to the emerging areas such as epigenetic regulation, microRNAs (miRNAs) and the cancer stem cells (CSCs), nutraceuticals initially appeared out of place. However, research investigations over the last several years have slowly but firmly presented evidence that supports a relevance of these agents in modern day research. While nutraceuticals are increasingly being realized to alter miRNA/CSCs expression and function, the molecular mechanism(s) are not very clearly understood. Epigenetic regulation is one mechanism by which these agents exert their anticancer effects. In this focused mini review, we summarize our current understanding of epigenetic regulation of miRNAs and CSCs by nutraceuticals. We discuss both direct and indirect evidences that support such an activity of these compounds. PMID:24272883

The impact of trisomy 21 on foetal haematopoiesis.

PubMed

Roberts, Irene; O'Connor, David; Roy, Anindita; Cowan, Gillian; Vyas, Paresh

2013-12-01

The high frequency of a unique neonatal preleukaemic syndrome, transient abnormal myelopoiesis (TAM), and subsequent acute myeloid leukaemia in early childhood in patients with trisomy 21 (Down syndrome) points to a specific role for trisomy 21 in transforming foetal haematopoietic cells. N-terminal truncating mutations in the key haematopoietic transcription factor GATA1 are acquired during foetal life in virtually every case. These mutations are not leukaemogenic in the absence of trisomy 21. In mouse models, deregulated expression of chromosome 21-encoded genes is implicated in leukaemic transformation, but does not recapitulate the effects of trisomy 21 in a human context. Recent work using primary human foetal liver and bone marrow cells, human embryonic stem cells and iPS cells shows that prior to acquisition of GATA1 mutations, trisomy 21 itself alters human foetal haematopoietic stem cell and progenitor cell biology causing multiple abnormalities in myelopoiesis and B-lymphopoiesis. The molecular basis by which trisomy 21 exerts these effects is likely to be extremely complex, to be tissue-specific and lineage-specific and to be dependent on ontogeny-related characteristics of the foetal microenvironment. © 2013.

The impact of trisomy 21 on foetal haematopoiesis

PubMed Central

Roberts, Irene; O'Connor, David; Roy, Anindita; Cowan, Gillian; Vyas, Paresh

2015-01-01

The high frequency of a unique neonatal preleukaemic syndrome, Transient Abnormal Myelopoiesis (TAM), and subsequent acute myeloid leukaemia in early childhood in patients with trisomy 21 (Down syndrome) points to a specific role for trisomy 21 in transforming foetal haematopoietic cells. N-terminal truncating mutations in the key haematopoietic transcription factor GATA1 are acquired during foetal life in virtually every case. These mutations are not leukaemogenic in the absence of trisomy 21. In mouse models, deregulated expression of chromosome 21-encoded genes is implicated in leukaemic transformation, but does not recapitulate the effects of trisomy 21 in a human context. Recent work using primary human foetal liver and bone marrow cells, human embryonic stem cells and iPS cells cells shows that prior to acquistion of GATA1 mutations, trisomy 21 itself alters human foetal haematopoietic stem cell and progenitor cell biology causing multiple abnormalities in myelopoiesis and B-lymphopoiesis. The molecular basis by which trisomy 21 exerts these effects is likely to be extremely complex, to be tissue- and lineage-specific and to be dependent on ontogeny-related characteristics of the foetal microenvironment. PMID:23932236

Neuroprotection and neurorestoration as experimental therapeutics for Parkinson's disease.

PubMed

Francardo, Veronica; Schmitz, Yvonne; Sulzer, David; Cenci, M Angela

2017-12-01

Disease-modifying treatments remain an unmet medical need in Parkinson's disease (PD). Such treatments can be operationally defined as interventions that slow down the clinical evolution to advanced disease milestones. A treatment may achieve this outcome by either inhibiting primary neurodegenerative events ("neuroprotection") or boosting compensatory and regenerative mechanisms in the brain ("neurorestoration"). Here we review experimental paradigms that are currently used to assess the neuroprotective and neurorestorative potential of candidate treatments in animal models of PD. We review some key molecular mediators of neuroprotection and neurorestoration in the nigrostriatal dopamine pathway that are likely to exert beneficial effects on multiple neural systems affected in PD. We further review past and current strategies to therapeutically stimulate these mediators, and discuss the preclinical evidence that exercise training can have neuroprotective and neurorestorative effects. A future translational task will be to combine behavioral and pharmacological interventions to exploit endogenous mechanisms of neuroprotection and neurorestoration for therapeutic purposes. This type of approach is likely to provide benefit to many PD patients, despite the clinical, etiological, and genetic heterogeneity of the disease. Copyright © 2017. Published by Elsevier Inc.

PPAR agonists as therapeutics for CNS trauma and neurological diseases

PubMed Central

Mandrekar-Colucci, Shweta; Sauerbeck, Andrew; Popovich, Phillip G.; McTigue, Dana M.

2013-01-01

Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Specifically, injury or disease elicits acute infiltration and activation of immune cells, death of neurons and glia, mitochondrial dysfunction, and the secretion of substrates that inhibit axon regeneration. In some diseases, inflammation is chronic or non-resolving. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many pre-clinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated. In this review we discuss current literature supporting the role of PPAR activation as a therapeutic target for treating traumatic injury and degenerative diseases of the CNS. PMID:24215544