Wednesday, 20 September 2017

All mouth and no ears: Settlers with Opinions

The Conversation Academic rigor, journalistic flair September 19, 2017 6.34pm EDT The Scream, by Kent Monkman (2016), is part of a traveling exhibition this year on colonized Canada: Shame And Prejudice: A Story Of Resilience. Kent Monkman Author Daniel Heath Justice Professor and Canada Research Chair in Indigenous Literature and Expressive Culture, University of British Columbia Disclosure statement Daniel Heath Justice receives funding from SSHRC, as he holds the Canada Research Chair in Indigenous Literature and Expressive Culture. Partners University of British Columbia It’s a depressingly common experience for Indigenous people in this country. It happens on a daily basis: At work with colleagues, in encounters with strangers, in news commentaries, in social media exchanges and at parties when we just want to relax. It’s almost a guarantee that any time an Indigenous issue receives public attention, we will be subjected to the pronouncements of Settlers with Opinions. Recently we have had to deal with the misinformed public opinions of a Canadian senator who celebrated Canada’s assimilationist policies in an open letter and who in the spring cited fake news in her defence of residential schools. She is just one of many with inaccurate and distorted opinions, including editors of influential Canadian media and men serving in the Canadian military. Settlers with Opinions are far from those fair-minded non-Indigenous folks who bring generosity and humility to their interactions with Indigenous peoples: thoughtful professionals who do their research and build meaningful connections, curious and committed students in my Indigenous Studies classes, sincere strangers with challenging questions and friends who trust that their gaps in knowledge won’t be shamed. Regardless of political affiliation — whether sneering Conservatives or head-patting Liberals — Settlers with Opinions are of an entirely different type. It’s attitude, not identity, that distinguishes the two. Mostly white and often — though not always — men, these apologists for colonialism can be readily identified by their relentless, resentful Certainty, detached from informed understanding or even empathy. Opinions without knowledge Researchers such as Kim TallBear offer strong critique of the ways that scientific racism informs public misunderstandings of Indigenous identity. The Settler with Opinions doesn’t just have thoughts about these matters: He has important Opinions, and he insists on subjecting us to them. He is generally not trained in any relevant profession or scholarly discipline that would give some credibility to his assertions, nor is he even a particularly careful or selective reader. When more academically inclined, he typically adheres to long discredited 19th-century pseudo-scientific theories. Nor does he have meaningful personal experience or relationships that might provide understanding of Indigenous matters. Maybe he lived near a reserve or worked with an Indigenous person once. Maybe he’s among the growing ranks of settlers who has found an anonymous Indian in the family tree that seems to magically authorise commentary on all things Indigenous without accountability to a living community. The Settler with Opinions believes herself to be above critique or even questioning, as she is The One with All the Answers. She assures us she knows our problems better than we do. Her lack of knowledge is no obstacle: She claims her ignorance as a badge of honour, for it confirms that she’s Objective. Her solutions are a tiresome regurgitation of devastating imposed policies that have failed time and again. But because she doesn’t do any careful research, because she feels no need to actually engage with people who’ve experienced these things firsthand, she’s unfamiliar with this long and ugly history. We’ve heard the exact same vacuous Opinions and ill-formed stereotypes a thousand times before. Our parents and grandparents and many generations before us heard them, too, and they resisted them as best they could. They had to deal with Settlers with Opinions in their times, too. Reconciliation without truth There’s nothing the Settler with Opinions won’t opine upon, no matter too intimate or too painful for him to intrude. He loves to weigh in on matters of Indigenous identity. He knows next to nothing about the complex internal processes of belonging or the ongoing and destructive legacies of colonial intrusion into these most private matters. Yet this never stops him; it seems the less he knows, the more confident he is that we’ve got it all wrong no matter where we stand. He has no investment in Indigenous women’s issues of any kind and no particular concern about their well-being. But as a firm advocate of patriarchy and its values, he’s quick to offer a blaming assessment of their sexualities, gendered expressions and even their bodies. He’s rarely, if ever, read a book by an Indigenous writer. Yet he can explain, in detail, how much they’re lacking in literary quality, scope, sophistication and universal appeal. The Settler with Opinions is allergic to all but the most partial context, and only that which justifies her pre-existing biases. She dismisses cultural appropriation, but is the first to defend her intellectual property rights. She insists Indigenous land activists should be held accountable to Canadian law but is unfamiliar with Indigenous legal orders that predate those of Canada. She’s predictably silent about the centuries of legalized racism that continue to strip us of our lands and imperil our relations. And she has no clue of the obligations we have to one another or to our other-than-human kin. She dismisses the Truth and Reconciliation Commission as a guilt-inducing waste of time and money. She waxes poetic on the “good intentions” of those who empowered this system of child-theft and abuse and rape. She’s not particularly concerned with the horrors that were visited upon little bodies, hearts and minds as long as their souls were saved by their charitable Christian tormentors. She says we shouldn’t judge the past by today’s politically correct standards. But she refuses to acknowledge the contesting voices of the past, and she refuses to see the privileging of only non-Indigenous perspectives as a political decision with real consequences for real people. She’s fine with talking reconciliation as long as the status quo doesn’t change. It’s the Truth part of the TRC she simply can’t abide and won’t take any effort to learn. Children in Friendly Cove, B.C.: Indigenous peoples have always resisted oppressive policies. CC BY Conversations without exchange When we do counter his shallow stereotypes with voluminous evidence alongside personal or familial experience, when we complicate his simplistic savage and civilized binaries with more accurate and more complex realities, the Settler with Opinions shifts tactics. He’s a master at dismissal, tone policing, derailing and evasion. When we actually want to have a real discussion, the Settler with Opinions changes the topic. A real conversation or thoughtful exchange is the last thing he wants. He prefers an audience for his singular settler monologue locked on generational repeat. Seeing Red outlines a long history of racism and racist misrepresentation in Canadian media. For years he’s insisted that we didn’t have the professional or scholarly credentials to legitimately respond to his Opinions. When we earn them, he sniffs about the academy’s diminished standards, the insularity of the Ivory Tower elite, the decline of traditional journalism. And he certainly has no patience with community-based knowledge holders whose deep expertise comes from enduring relationships and experience with the land. He’s quick to condemn terms like “settler,” “colonialism,” and “genocide,” insisting that they’re uncivil and ill-applied. He insists the bloody reality thus named is too alienating. Such forthright language makes people like him feel uncomfortable. His comfort is the most important thing when discussing the oppression of Indigenous peoples. We discuss the complicated relationships and emotionally challenging entanglements of belonging and kinship; she responds with simplistic soundbites about blood quantum and identity policing. We critique the power inequities in appropriation; he condemns our delusional fixation on cultural purity. We confront the devastating impacts of colonial policies on our nations’ diverse and complex languages, literatures, technologies, political structures and social systems; she gives us a treatise on how her ancestors so generously dragged our benighted ancestors into civilisation. And it’s not just the past: The Settler with Opinions finds invalidating fault in every facet of our 21st century being. Raised outside of community? Illegitimate. Raised in community? Anti-modern romantic. Of mixed heritage? Inauthentic. Phenotypically Indigenous? Retrograde. Racism without accountability He may be peddling the ugliest, most antiquated ideas and beliefs about Indigenous peoples, but if we dare to even hint that these are racist he’ll rage about how he’s the victim of reverse racism. He insists that his perspective is unjustly marginalized, that Indigenous people are the real bigots causing racial strife, that we need to stop being so unreasonable and just embrace his rightness — no matter how wrong it may be. And, oh, if we have other things to do than respond to him, beware, because the Settler with Opinions insists on being the focus of every bit of our attention at all times. He insists that we not only listen to him but we also give him all our time and energy to reply to every single point he brings forward, address every tired argument, every snide comment, every sloppy stereotype and demeaning insult with servile adoration. When we fail to appreciate or acknowledge his self-evident brilliance, he hurls insults about our substandard intellectual capabilities and rails about our bubble mentality and inability to engage contrary voices. It hardly matters that we’ve been responding to such voices for a long, long time, to little evident effect, and that we have busy lives that don’t always include being his audience. But when we point that out, he gets mean. Excerpt from the 1920 testimony of Duncan Campell Scott, the. deputy superintendent general of Indian affairs, to the Special Parliamentary Committee of the House of Commons. The Critical Thinking Consortium We grow tired of the condescending dismissals, the racist epithets, the physical threats, the demeaning insistence that we’re subhuman and beneath contempt, the hypocritical evasions, the gleeful celebrations of our pain and loss, the relentless goading, the refusals to consider that we, too, have perspectives on our own being. When we fight back with experience, facts, and rightful anger, the Settler with Opinions feigns shock and quickly turns petulant. He’s every bit as comfortable in the position of whinging martyr as righteous crusader. Generations of resistance He wails about our violation of his free speech, our cruel mob mentality, our animalistic swarming of his supremely rational self. He dismisses us as irresponsible, unhinged, sociopathic: Savages in all but name. The Settler with Opinions becomes a remarkably sensitive soul when he’s the focus of public criticism. But he regularly turns a blind eye to the tidal wave of vitriol that Indigenous commentators experience on a regular basis — especially Indigenous women and transfolk who are regularly targeted with rape threats from his trollish supporters. It takes a particular level of courage to be an Indigenous person in Canada’s public sphere, especially online. He’s never been subjected to this kind of violence and bile, no matter how angry or frustrated we get. Resistance is crucial: About 1,000 Idle No More protesters demonstrate in Windsor, Ont., in 2013 to disrupt traffic to the country’s busiest border crossing. (THE CANADIAN PRESS/ Geoff Robins) Ultimately, it seems that Settlers with Opinions can only see Indigenous peoples through a lens of inherent deficiency. Their driving, desperate need for us and our ancestors to be not only inferior but utterly inhuman doesn’t actually have anything to do with us. It’s entirely about their fragile self regard. But knowing this truth doesn’t make them any more pleasant to endure. It doesn’t matter whether the decree comes from Beyak, Black, Wente, Blatchford, Kay, Gilmore, Widdowson, Murphy, an anonymous social media troll or that uncle at Thanksgiving dinner, the message is always the same: Shut up and assimilate. This is an old message and one responsible for incalculable misery. It was forced on our ancestors by churches, soldiers, policy makers, and everyday settler subjects who insisted they knew better and who insisted we should hate ourselves as much as they did. And it continues every day. For those like me, who were raised outside of our nations and have spent the better part of our lives working to undo internalised family shame and trauma while trying to learn our responsibilities to kin and community from afar, this message is particularly painful. We know its deep generational consequences all too well. Like all living human cultures, Indigenous peoples are fully part of the 21st century, but that’s not enough for Settlers with Opinions. They’ve decided we can’t be both Indigenous and part of the modern world. They insist we abandon the legacies, lands, languages, relations, commitments and complexities that have always rooted and sustained our nations. They insist we stop trying to rebuild what was destroyed, to give up restoring what’s been lost, to let go of what remains. They want us to simply shut up and disappear as distinct peoples with values and perspectives of our own. They give us a single option: to accept settler claims to cultural superiority no matter how illegitimate or false the justification may be. Worst of all, they expect us to turn our backs on generations of principled Indigenous resistance, the immeasurable sacrifices of our ancestors, and the continuing struggles of our nations and extended kin. And for what? For the dubious benefits of assimilation into an exploitative, murderous mainstream that has for generations so relentlessly insisted on and worked toward our nations’ disappearance. Then, at last, they would get to be right. Then there would be no one left to challenge the false mythology of settler sanctity or its ongoing devastations. Then there would be no one left to take up the hard work of righting relations with this wounded world. Thanks all the same, but that’s an offer we must continue to refuse.

Does Achillea millefolium extracts possess prokinetic effects on the bovine abomasum thourgh M3 muscarinic receptors?

Vet Res Forum. 2017 Spring; 8(2): 115–120. Published online 2017 Jun 15. PMCID: PMC5524548 Mojtaba Mohseni,1,* Masoud Maham,2 Bahram Dalir-Naghadeh,2 and Ghader Jalilzadeh-Amin2 1 DVSc Candidate, Department of Internal Medicine and Clinical Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran; 2 Department of Internal Medicine and Clinical Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. *Correspondence: Mojtaba Mohseni. DVM, DVSc Candidate, Department of Internal Medicine and Clinical Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. E-mail: Author information ▼ Article notes ► Copyright and License information ► Go to: Abstract Displacement of the abomasum is a common disease of the gastrointestinal tract in dairy cattle. Abomasal displacement has been associated with abomasal hypomotility. Therefore, it is necessary to identify effective therapeutic agents that stimulate abomasal motility in cattle. Yarrow (Achillea millefolium) is traditionally used as a folk remedy for treatment of human gastrointestinal complaints in the northwest of Iran. This study investigated the effects of A. millefolium extracts on abomasal smooth muscle preparations from healthy cattle. The A. millefolium extracts (3 to3000 mg L-1) contracted the isolated of smooth muscle in a concentration-dependent manner, with an effective threshold concentration of 30 mg L-1 (p < 0.05). The strongest contraction by A. millefolium aqueous extracts in a concentration of 3000 mg L-1 was observed and amounted to 124.90 ± 10.80% of the control treatment. This action was unaffected by pretreatment with hexamethonium and indomethacin, but strongly reduced by verapamil, atropine and 4-DAMP. The inhibiting effect of 4-DAMP and atropine suggesting that the effect of A. millefolium extracts is mediated at least partly by M3 muscarinic acetylcholine receptor. The results suggested that A. millefolium has the potential prokinetic effect that may prevent or alleviate dysfunctions of gastrointestinal motility. Key Words: Abomasal motility, Achillea millefolium, Organ bath, Prokinetic Go to: Introduction Impaired abomasal motility is common in dairy cattle and is suspected to play a major role in the occurrence of left displaced abomasum, abomasal volvulus and abomasal impaction in cattle.1,2 Abomasal motility decreases in many ailments, namely ketosis, hypocalcemia, hyperinsulinemia, and reduced insulin sensitivity that have been studied and reported in recent publications.3-7 Thus, it would be clinically helpful to identify effective prokinetic drugs that stimulate, coordinate and restore abomasal motility in cattle. The importance of the parasympathetic nervous system in the physiology of GI motility and in the pathophysiology of motility disorders has been described in cattle.8 In the cholinergic system, the main endogenous neurotransmitter, acetylcholine (ACh), activates G-protein coupled muscarinic receptors. Smooth muscle contraction in GI organs is the most important effect of the activation of muscarinic receptors located directly on smooth muscle cells or on the nerve cells of the GI nervous system.9 Several investigations have been carried out in characterizing muscarinic receptors in the digestive tract of cattle. In the bovine gut smooth muscle, it has been shown that mRNA transcripts and binding sites of M2 and M3 AChR subtypes are the most abundant with a ratio of 5:1.10 In the clinical setting, left-side displacement of the abomasum (LDA) in cows did not alter the extracellular components of M2 and M3 receptors in the GI tract, whereas receptor densities were lower in the intestinal wall (mainly duodenum) of cows with LDA.8 Bethanechol, a well-known prokinetic drug, induces contraction of smooth muscle cells by direct stimulation of muscarinic receptors. In vitro studies on smooth muscle preparations revealed a bethanechol-induced, contractility in muscle strips from the esophageal groove of calves11 and the abomasum of healthy cows.12 However, chemical drugs often have limitations such as serious adverse side effects.9 Therefore, herbal products may be an attractive alternative thanks to their lower risk their proved prokinetic effects.13-15 Achillea millefolium L. (Yarrow) which belongs to the Asteraceae family is one of the most widely used medicinal plants in the world.16 In West Azerbaijan (Iran) the aerial parts of the plant have been used traditionally to treat gastritis, cancer, hemorrhoids, vertigos, anemia, anorexia, dyspepsia, gastralgia, hemorrhage, dysmenorrhea and diarrhea.17 Preclinical studies indicate that yarrow may have anti-inflammatory, hepatoprotective, antinociceptive, anxiolytic and antimicrobial activities. Animal studies have also shown that it is generally safe and well tolerated.16 In Italy leaves of yarrow are used to make an ointment cooking them over a low heat with olive oil, talon, bee’s wax and egg yolk; this is applied locally to cure sores on bovines’ withers caused by yoke rubbing.18 In British Columbia, Canada, the extract of plant flowers has been used to treat diarrhea and gastritis in dogs and cats. It is given orally with a syringe or put in the drinking water.19 The main constituents of yarrow are volatile oils (sabinene, β-pinene, 1,8-cineole, artemisia ketone, linalool, α-thujone, β-thujone, camphor, borneol, fenchyl acetate, bornyl acetate, (E)-beta-caryophyllene, germacrene D, caryophyllene oxide, beta-bisabolol, delta-cadinol, chamazulene); flavonoids (apigenin- and luteolin-7-glycosides, and rutin); and alkaloids.20 In the current study, we used extracts of yarrow to assess its reported prokinetic action on smooth muscles in the rodent and human gastrointestinal tract,21 to investigate their regulatory effects on contractions of the smooth muscles of the bovine abomasum, and also elucidate its mechanism of action. Go to: Materials and Methods Chemicals. Acetylcholine chloride (ACh), atropine sulfate, hexamethonium, indomethacin, verapamil hydrochloride and 4-DAMP were purchased from Sigma Chemicals Co. (St Louis, USA). Calcium chloride, potassium chloride, sodium chloride, glucose, magnesium sulfate, potassium dihydrogen phosphate, sodium bicarbonate, ethanol and chloroform were obtained from Merck (Darmstadt, Germany). Plant material and extraction. Aerial parts of A. millefolium were collected from the northwest of Iran in 2015. The plant was identified in the Department of Botany, Tarbiat Modarres University of Tehran, Tehran, Iran and a sample was deposited in the herbarium of the Department of Medicinal and Industrial Plants, Urmia University, with the voucher number of 5374. The plant material was cleaned, shade-dried and coarsely grounded. The powdered material was extracted with 70% ethanol by cold maceration for three days with occasional shaking. It was filtered through a muslin cloth and then through a Whatman qualitative grade 1 filter paper (Sigma). This procedure was repeated twice and the combined filtrate was evaporated in a rotary evaporator to obtain hydroalcoholic extract of A. millefolium. A part of this extract was used in the pharmacological studies and the other part was used for the fractionation. The extract was suspended in distilled water and extracted with chloroform. The mixture was allowed to separate into two layers. The upper layer (aqueous fraction) was again taken into a separating funnel; ethyl acetate was added to it, separated and evaporated with the rotary evaporator to get the ethyl acetate fraction. The remaining lower layer was collected and evaporated to obtain the A. millefolium aqueous extract (AMAE). Preparation of smooth muscle and data acquisition. Tissue samples were collected from routinely slaughtered Holstein crossbred dairy cows (4 to 8 years old; n = 18) with no previous history of abomasal displacement or other abomasal disorders. The abomasum was removed within 20 min after stunning. Full-thickness specimens were harvested from the body of the abomasum by dissecting a rectangular piece of tissue (6 × 15 cm) from the location. Tissue specimens were immediately rinsed with cooled (4 ˚C) Krebs solution (composition (mM): NaCl, 118.00; KCl, 4.75; MgSO4, 1.20; KH2PO4, 1.20; CaCl2, 2.50; NaHCO2, 25.00 and glucose, 11.50). Specimens were stored in 1 L of cooled (4 ˚C) Krebs solution that had been oxygenated (95% O2 and 5% CO2) for 1 hr; and were transported from the slaughterhouse to the laboratory within 15 min. The whole pieces of tissue were placed in a petri dish filled with Krebs solution at room temperature and the mucosa was carefully removed from the muscle layers, and tissue strips (15 × 2 mm) were cut from the abomasal body muscle fibers. The abomasal strips were mounted in separated 25 mL chambers, maintained at 37 ˚C in Krebs solution, and gassed continuously with a mixture of 95% O2 and 5% CO2. One end of each strip was fixed to the bottom of the chamber, and the other end was attached to an isometric muscle transducer (model TRI 202P; PanLab, Barcelona, Spain) coupled to bridge amplifier (model ML224; AD Instruments, Castle Hill, Australia) and data acquisition PowerLab system (model ML870; AD Instruments) using Labchart software (version 8.0, AD instruments). Specimens were allowed to equilibrate in the organ bath for 1 hr, whereby muscle tension was preset to 2 g in two steps (1 g each) at 10 min intervals and during this time Krebs solution was replaced every 15 min with fresh solution. All specimens were tested for functional viability prior to and after all experiments by the addition of 1 M acetylcholine to the organ bath. The dose-response curves to determine the effect of acetylcholine were obtained by exposing the preparation to increasing concentrations added to the bath (2 min to each concentration). Then the submaximal (inducing responses approximately 70% of the maximum) concentration was determined for each of the strips. Strips producing three consistent repeatable responses to submaximal concentration of acetylcholine were used. After removal of acetylcholine through wash out, the abomasum responses were observed in the presence of increasing cumulative concentrations of A. millefolium aqueous and hydroalcoholic extracts (3 to 3000 mg L-1). To assess the possible mechanisms underlying the contractile effect of the aqueous fraction on abomasal strips, atropine, a muscarinic receptor blocker (10 µM); hexamethonium, a nicotinic nACh (NN) receptor anta-gonist (10 µM); indomethacin, a prostaglandin synthesis inhibitor (10 µM); and 4-DAMP, a muscarinic M3 receptor antagonist (10 µM) and verapamil, a calcium channel blocker (0.1 µM) was added to the organ bath 10 min prior to the addition of the extract (3 to 3000 mg L-1). Statistical analysis. Data were examined graphically for assumptions of normal distribution and homogeneity of variation. Nonparametric statistical test was used for analysis because the assumptions were not met normal distribution. The Friedman repeated measures analysis of variance on ranks was used to compare results in strength of contractions between different concentrations of the extract. Overall p < 0.05 was considered significant. Pair-wise comparisons between each treatment group (concentration) versus control group were made using Dunnett's Method. Results are expressed as medians and interquartile ranges (25th - 75th percentiles). Data were analyzed using SigmaPlot for windows (version 12.3; Systat Software, Inc. San Jose, USA). Go to: Results We tested 72 specimens by the use of Acetylcholine chloride to determine functional viability and only six specimens did not respond to stimulation with Acetylcholine chloride. All 66 specimens tested at the end of the recording period had the expected response to Acetylcholine chloride and showing that the muscle was not damaged by non-specific action. Acetylcholine (1 to 10 µM) caused a concentration-dependent contraction of the cattle abomasum. The solvent as a control (distilled water), did not exert an effect on basal tonus of any preparations of cattle abomasum. The A. millefolium aqueous and hydroalcoholic extracts (3 to 3000 mg L-1) contracted the isolated strips of cattle abomasum smooth muscle in a concentration-dependent manner, with an effective threshold concentration of 30 mg L-1 (p < 0.05, Fig. 1) but treatment of tissue strips with 3 and 10 mg L-1 of A. millefolium extracts did not show any significant difference with the control. A typical trace, showing the effect of the A. millefolium aqueous extract (3 to 3000 mg L-1) is covered in Figure 2A. Fig. 1. Fig. 1. Box plots for effects of A. millefolium aqueous extract (n = 8) (A) and hydroalcoholic extract (n = 8) (B) on basal tonus of healthy cattle abomasal preparations. Each box represents the central 50% of the values, the horizontal line within each box represents ... Fig. 2 Fig. 2 Basal contractions and dose dependent response of abomasal smooth muscle to AMAE (A). Inhibitory effects of atropine (B), 4-DAMP (C), and verapamil (D) on the AMAE-induced contractions of abomasal smooth muscle When the organ bath was drained and Krebs was added, there was a rapid relaxation of the muscle to baseline of resting tension. Atropine at 10 µM, concentration did not affect the spontaneous smooth muscle contractions but abolished the contractile effect of Ach. Treatment of the tissues with atropine (10 µM) completely abolished AMAE induced smooth muscle contractions (Fig. 2B). Furthermore, the M3 muscarinic receptor antagonist 4-DAMP (10 µM) revealed an inhibition of contractions caused by AMAE (Fig. 2C), while either hexamethonium (10 µM) or indomethacin (10 µM) had no impact (data not shown). Verapamil at the bath concentration of 0.1 µM dramatically inhibited the contractile amplitude and tension induced by AMAE (Fig. 2D). Go to: Discussion The main findings of this study were that the A. millefolium extracts induced a significant increase in contractility of smooth muscle preparations of abomasum. The spasmogenic effect of aqueous extract was completely abolished in the tissues pretreated with atropine, similar to that of ACh. Results of this study confirmed the presence of cholinergic constituent(s) in the extract of the plant responsible for the spasmogenic response. Acetylcholine ,a neurotransmitter of the parasympathetic nervous system, has an important role in abomasal motility,22 and its action is mediated by the activation of muscarinic receptors, whereas atropine is a muscarinic receptor blocker.12 Our findings were in agreement with a previous study that demonstrated the aqueous extract of dried flower heads of yarrow exerted a direct spasmogenic effect on mouse and human gastric antrum.21 When the stimulant effect of AMAE was studied in the presence of hexamethonium, a ganglion blocker or indomethacin, a prostaglandin synthesis inhibitor, it remained unchanged, suggesting the presence of ACh-like constituents independent of nicotine receptors activation or prostaglandin synthesis inhibition. Acetylcholine, the main endogenous neurotransmitter in the cholinergic system, causes a contraction of the smooth muscle layers in the forestomach and abomasum through activation of muscarinic receptors8,23 located directly on smooth muscle cells or nerve cells of enteric nervous system.24 It has been demonstrated that M3 mAChRs play a predominant role in the mediation of contraction in smooth muscle preparations, even though M2 mAChRs were detected at higher density than M3 mAChRs.25,26 Regarding in these information, we examined whether AMAE-induced contraction was mediated, at least, by activation of the M3 muscarinic receptors and observed that the muscarinic M3 receptor-preferring antagonist, 4-DAMP, completely blocked the AMAE-induced contractions. Although it has been suggested that the extent of contribution of the muscarinic M3 receptors differs with the type of smooth muscles and the species of animals,27 we consider that AMAE may have high affinity with the muscarinic M3 receptors, Accordingly the contractile response of the abomasal smooth muscle to AMAE may chiefly result from the activation of muscarinic M3 receptors. However, to clearly understand these speculations, further studies are needed to elucidate the pharmacological affinity of AMAE with the muscarinic receptor subtypes. Pretreatment of tissues with verapamil, a standard calcium channel blocker, inhibited muscle contractions induced by AMAE, confirming the action of extract on abomasal motility was medicated by Ca2+ influx. The M3 muscarinic receptor is coupled to Gq-type G proteins, resulting in the activation of the second messengers inositol trisphosphate which induces Ca2+ release from intracellular Ca2+.28 In smooth muscle cells, increase in cytoplasmic calcium concentration is the primary stimulus for contraction, which is generally the result of both release of intracellular stored calcium and the influx of extracellular calcium.29 The main pathway for Ca2+ entry into intestinal smooth muscle cells is through L-type Ca2+ channels. Verapamil is a calcium channel blocker that has been used to promote the relaxation of smooth muscle cells by inhibiting calcium influx through calcium channels and calcium release from intracellular stores.30,31 In a previous study, the chemical composition of yarrow has been analyzed in detail and extracts of this plant have been demonstrated to contain a number of pharmacological active ingredients, including alkaloids such as choline and flavonoids such as rutin and apigenin.21 Borrelli et al. also indicated that choline, is the chemical ingredient of yarrow responsible for the gastric contractile effect. Further studies are warranted to investigate the in vivo effects of AMAE in animals suffering from LDA. Go to: Acknowledgements This study was supported by the Faculty of Veterinary Medicine, Urmia University. The authors would like to thank Dr. Amin Mamaghani for his valuable contributions. Go to: References 1. Doll K, Sickinger M, Seeger T. New aspects in the pathogenesis of abomasal displacement. Vet J. 2009;181:90–96. [PubMed] 2. Ozturk AS, Guzel M, Askar TK, et al. Evaluation of the hormones responsible for the gastrointestinal motility in cattle with displacement of the abomasum; ghrelin, motilin and gastrin. Vet Rec. 2013;172:636. [PubMed] 3. Chapinal N, Carson M, Duffield TF, et al. The association of serum metabolites with clinical disease during the transition period. J Dairy Sci. 2011;94:4897–4903. [PubMed] 4. Mokhber Dezfouli M, Eftekhari Z, Sadeghian S, et al. Evaluation of hematological and biochemical profiles in dairy cows with left displacement of the abomasum. Comp Clin Pathol. 2013;22:175–179. [PMC free article] [PubMed] 5. Mercadante PM, Ribeiro ES, Risco C, et al. Associations between pregnancy-associated glycoproteins and pregnancy outcomes, milk yield, parity, and clinical diseases in high-producing dairy cows. J Dairy Sci. 2016;99:3031–3040. [PubMed] 6. Suthar VS, Canelas-Raposo J, Deniz A, et al. Prevalence of subclinical ketosis and relationships with postpartum diseases in European dairy cows. J Dairy Sci. 2013;96:2925–2938. [PubMed] 7. Dhakal K, Tiezzi F, Clay JS, Maltecca C. Inferring causal relationships between reproductive and metabolic health disorders and production traits in first-lactation US Holsteins using recursive models. J Dairy Sci. 2015;98:2713–2726. [PubMed] 8. Ontsouka EC, Niederberger M, Steiner A, et al. Binding sites of muscarinic and adrenergic receptors in gastro-intestinal tissues of dairy cows suffering from left dis-placement of the abomasum. Vet J. 2010;186:328–337. [PubMed] 9. Steiner A. Modifiers of gastrointestinal motility of cattle. Vet Clin North Am Food Anim Pract. 2003;19:647–660. [PubMed] 10. Stoffel MH, Monnard CW, Steiner A, et al. Distribution of muscarinic receptor subtypes and interstitial cells of Cajal in the gastrointestinal tract of healthy dairy cows. Am J Vet Res. 2006;67:1992–1997. [PubMed] 11. Barahona MV, Sanchez-Fortun S, San Andres MD, et al. Acetylcholinesterase histochemistry and functional characterization of the muscarinic receptor mediating the contraction of the bovine oesophageal groove. J Auton Pharmacol. 1997;17:77–86. [PubMed] 12. Buehler M, Steiner A, Meylan M, et al. In vitro effects of bethanechol on smooth muscle preparations from abomasal fundus, corpus, and antrum of dairy cows. Res Vet Sci. 2008;84:444–451. [PubMed] 13. Nam Y, Lee JM, Wang Y, et al. The effect of Flos Lonicerae Japonicae extract on gastro-intestinal motility function. J Ethnopharmacol. 2016;179:280–290. [PubMed] 14. Brierley SM, Kelber O. Use of natural products in gastrointestinal therapies. Curr Opin Pharmacol. 2011;11:604–611. [PubMed] 15. Oka T, Okumi H, Nishida S, et al. Effects of Kampo on functional gastrointestinal disorders. Biopsychosoc Med. 2014;8:5. [PMC free article] [PubMed] 16. Akram M. Minireview on Achillea millefolium Linn. J Membr Biol. 2013;246:661–663. [PubMed] 17. Miraldi E, Ferri S, Mostaghimi V. Botanical drugs and preparations in the traditional medicine of West Azerbaijan (Iran) J Ethnopharmacol. 2001;75:77–87. [PubMed] 18. Uncini Manganelli RE, Camangi F, Tomei PE. Curing animals with plants: traditional usage in Tuscany (Italy) J Ethnopharmacol. 2001;78:171–191. [PubMed] 19. Lans C, Turner N, Khan T, et al. Ethnoveterinary medicines used to treat endoparasites and stomach problems in pigs and pets in British Columbia, Canada. Veterinary parasitology. 2007;148:325–340. [PubMed] 20. Orav A, Arak E, Raal A. Phytochemical analysis of the essential oil of Achillea millefolium L. from various European Countries. Natural product research. 2006;20:1082–1088. [PubMed] 21. Borrelli F, Romano B, Fasolino I, et al. Prokinetic effect of a standardized yarrow (Achillea millefolium) extract and its constituent choline: studies in the mouse and human stomach. Neurogastroenterol Motil. 2012;24:164–171. [PubMed] 22. Michel A, Mevissen M, Burkhardt HW, et al. In vitro effects of cisapride, metoclopramide and bethanechol on smooth muscle preparations from abomasal antrum and duodenum of dairy cows. J Vet Pharmacol Ther. 2003;26:413–420. [PubMed] 23. Poole DP, Littler RA, Smith BL, et al. Effects and mechanisms of action of the ergopeptides ergotamine and ergovaline and effects of peramine on reticulum motility of sheep. Am J Vet Res. 2009;70:270–276. [PubMed] 24. Ontsouka EC, Steiner A, Bruckmaier RM, et al. Quantitative mRNA analysis of muscarinic acetylcholine receptors in the intestine of dairy cows with spontaneous caecal dilatation-dislocation. Vet J. 2009;180:259–261. [PubMed] 25. Eglen RM. Muscarinic receptor subtype pharmacology and physiology. Prog Med Chem. 2005;43:105–136. [PubMed] 26. Ehlert F, Pak K, Griffin M. Muscarinic agonists and antagonists: effects on gastrointestinal function. In: Fryer AD, Christopoulos A, Nathanson NM, editors. Muscarinic Receptors. Springer: 2012. pp. 343–374. 27. Barocelli E, Ballabeni V, Chiavarini M, et al. Regional differences in motor responsiveness to antimuscarinic drugs in rabbit isolated small and large intestine. Pharmacol Res. 1995;31:43–48. [PubMed] 28. Unno T, Matsuyama H, Sakamoto T, et al. M(2) and M(3) muscarinic receptor-mediated contractions in longitudinal smooth muscle of the ileum studied with receptor knockout mice. Br J Pharmacol. 2005;146:98–108. [PMC free article] [PubMed] 29. Sanders KM, Koh SD, Ro S, et al. Regulation of gastrointestinal motility-insights from smooth muscle biology. Nat Rev Gastroenterol Hepatol. 2012;9:633–645. [PMC free article] [PubMed] 30. Lyford GL, Farrugia G. Ion channels in gastrointestinal smooth muscle and interstitial cells of Cajal. Curr Opin Pharmacol. 2003;3:583–587. [PubMed] 31. Sanders KM, Kito Y, Hwang SJ, et al. Regulation of gastrointestinal smooth muscle function by interstitial cells. Physiology. 2016;31:316–326. [PMC free article] [PubMed] Articles from Veterinary Research Forum are provided here courtesy of Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

SCIENTIFIC NAME: Urtica dioica FAMILY NAME: Urticaceae COMMON NAME: stinging nettle, nettles

Food as Medicine: Kiwifruit (Actinidia deliciosa, Actinidiaceae)

HerbalEGram: Volume 14, Issue 7, July 2017 Editor’s Note: Each month, HerbalEGram highlights a conventional food and briefly explores its history, traditional uses, nutritional profile, and modern medicinal research. We also feature a nutritious recipe for an easy-to-prepare dish with each article to encourage readers to experience the extensive benefits of these whole foods. With this series, we hope our readers will gain a new appreciation for the foods they see at the supermarket and frequently include in their diets. The basic materials for this series were compiled by dietetic interns from Texas State University in San Marcos and the University of Texas at Austin through the American Botanical Council’s (ABC’s) Dietetic Internship Program, led by ABC Education Coordinator Jenny Perez. We would like to acknowledge Perez, ABC Special Projects Director Gayle Engels, and ABC Chief Science Officer Stefan Gafner, PhD, for their contributions to this project. By Hannah Baumana and Rachel Powersb a HerbalGram Associate Editor b ABC Dietetics Intern (Texas State, 2017) Overview Kiwifruit (Actinidia deliciosa, Actinidiaceae), also known by the less common name “Chinese gooseberry,” is one of 50 known species within the genus Actinidia.1 These species are climbing, woody vines with large, heart-shaped leaves and cream-colored flowers that bloom in the spring. The flowers are dioecious, with male and female blossoms found in separate individuals. The kiwifruit matures in early winter and typically has brown fuzzy skin. Depending on the species, the flesh is either green or yellow, but all species are filled with small black, edible seeds.1 While A. deliciosa accounts for about 90% of kiwifruit in international trade, two other species are cultivated and sold commercially: A. chinensis and A. arguta.2 Actinidia deliciosa is the common green kiwifruit.3 The most common cultivar of A. chinensis is “Hort16A,” known by the brand name ZESPRI, or “gold kiwifruit.”4 Actinidia arguta is referred to as “baby kiwi” or “grape kiwi” due to the small size of its fruits.2 Actinidia species are native to southwestern China, but they are now cultivated in New Zealand, the United States, Italy, France, Chile, and Japan.5 Phytochemicals and Constituents Kiwifruit provides fiber, potassium, folate, phosphorus, copper, and vitamins A, C, E, and K.3,6 In fact, one kiwifruit provides more than the Recommended Dietary Allowance (RDA) of vitamin C for adults and almost 35% of the RDA of vitamin K. Vitamin C has numerous health benefits, including anticarcinogenic and immune-regulating properties.3,7 In addition, it plays a role in the formation of collagen, a major component of connective tissue, skin, and bones. Vitamin C intake also has been shown to help mitigate a number of conditions, including cardiovascular disease and inflammation.8 Vitamin E is an antioxidant that stops the oxidation of low-density lipoprotein (LDL) cholesterol and protects cell membranes against damage caused by reactive oxygen species.9 Vitamin E also helps maintain the structure and function of skeletal, cardiac, and smooth muscles. Vitamin K regulates blood clotting, aids in the transfer of calcium through the body, and supports bone health, reducing the risk of osteoporosis and bone fractures due to age.10 Kiwifruit is also a good source of fiber, which contributes to its laxative effect. Additionally, the lignins in cellulose (a form of dietary fiber) are believed to have antimutagenic properties due to their ability to increase the adsorption of aromatic amines in the gut, thus preventing them from entering the blood stream. Aromatic amines can act as carcinogens after they have been metabolized by the liver.3 One of the interesting compounds present in kiwifruit is actinidin, an enzyme that helps to hydrolyze proteins. Due to the actinidin content of kiwifruit, other fruits and dairy products will soften or curdle upon prolonged contact with the chopped fruit, so kiwifruit should be added at the last minute to fruit salads and other mixed preparations. Actinidin has been shown to improve digestion by assisting with protein digestion and digestive motility.11 Kiwifruit contains numerous other bioactive compounds, including organic acids, plant pigments, and polyphenols. The primary organic acid in kiwi is citric acid, but it also contains malic, quinic, gallic, and oxalic acids. Organic acids provide the fruits with significant antioxidant properties. Some of the plant pigments present in kiwifruit include carotenoids and chlorophylls, and some cultivars also contain anthocyanins.11 The carotenoids include beta-carotene, lutein, violaxanthin, and 9’-cis-neoxanthin.3 When compared with other commonly consumed fruits, kiwifruit is the richest source of lutein, which is a carotenoid that is highly concentrated in the macula of the eye and is associated with lowering risk of cataracts. All Actinidia species contain chlorophylls a and b, but levels are much lower in the gold kiwi variety. Some kiwifruits also contain anthocyanins, but they are not a significant component of the antioxidant capacity of the fruit. Glutathione is another important antioxidant present in kiwifruit, and it not only prevents oxidative damage of cells but also helps to keep vitamins C and E in their active form, regenerating their antioxidant capacities.11 Historical and Commercial Uses Kiwifruit is featured in Chinese literature dating back to the 15th century.12 The kiwifruit was originally called mi hou tao, or “monkey peach,” because monkeys would eat the fruit in the wild.4 Traditionally, both the root and the fruit of A. chinensis were used in traditional Chinese medicine and are known as xiao yang tao. The root of A. chinensis contains antiangiogenic phytochemicals including triterpenes, polyphenols, and anthraquinones, and it has been noted in the Chinese pharmacopeia as being useful for treating many diseases, such as stomach, rectal, and breast cancers, as well as hepatitis viral infections.12-14 The fruit of A. chinensis was used as a juice to quench thirst, aid digestion, clear heat, and reduce irritability, inflammation, and vomiting.3,14 Other Actinidia species were used for their therapeutic effects as well. Historically, A. macrosperma was used to stimulate the immune system and A. polygama was used as an anti-inflammatory agent and to counteract allergies due to its anti-asthmatic effect.3,15 Modern Research Clinical trials for kiwifruit primarily have focused on its effects on the digestive, immune, and cardiovascular systems. Preliminary research has also investigated the antioxidant properties of kiwifruit and its possible inhibitory effect on cancerous cell growth. Gastrointestinal System Clinically, kiwifruit has been shown to have a laxative effect. Daily consumption of the fruit improved the frequency and ease of bowel movements and improved stool bulk and softness in healthy older adults.3 In another study, researchers found that daily kiwifruit intake relieved symptoms in subjects suffering from chronic constipation, with no reports of adverse effects like diarrhea.3 Additionally, a trial in healthy subjects who were not experiencing constipation found no adverse gastrointestinal effects from daily consumption of kiwifruit.16 These gastrointestinal benefits are attributed to the lubricating effects of kiwifruit’s pectin and the enzyme actinidin, which combine with the enzymes in the stomach and the small intestine to improve digestion.4 The pectin and fiber present in kiwifruits also function as prebiotics. Prebiotics help to modify the composition of the bacterial flora in the gut so that healthy bacteria are stimulated and harmful bacteria are suppressed. An in vitro study looked at the prebiotic effect of the pectin present in kiwifruit compared to other prebiotics like inulin, guar gum, and citrus pectin. The pectin in kiwifruit was more effective than these prebiotics in reducing the intestinal adhesion of harmful bacteria and increasing the adhesion of beneficial bacteria.17 In a mouse study on irritable bowel disease (IBD), extracts of both green and golden kiwifruit were administered, resulting in a potent anti-inflammatory effect. These results indicate that further research should be done exploring the medicinal properties of kiwifruits in the treatment of IBD.18 Antibacterial and Immunological Activity In an in vitro study, essential oil from A. macrosperma produced inhibitory effects against a number of common bacteria, including Escherichia coli and Staphylococcus aureus, as well as three common fungal species.3 In a mouse study, kiwifruit extract was shown to alter innate and acquired immunity when the mice were injected with cholera and diphtheria/tetanus vaccines.15 This could have implications for improving immunity in vaccinated individuals, particularly children and other high-risk populations. Other animal studies have shown that extracts of A. arguta may have anti-allergenic effects, implying a potential for the use of kiwi extracts as therapies for allergy conditions like bronchial asthma or eczema.3 A human trial observed the effects of daily intake of golden kiwifruit on both older adults (older than 65 years) and young children (ages 2-5) in relation to cold and flu-like illnesses. For the adults, those who ate four kiwifruits daily had symptoms for fewer days over the course of a cold than the adults who ate two bananas (Musa acuminata, Musaceae) daily. In the preschool children, the odds of getting a cold or the flu decreased by almost half in the children who ate two kiwifruits daily instead of one banana.4 Cardiovascular System There is some evidence that kiwifruit may have the ability to affect risk factors for cardiovascular disease, like blood pressure, plasma triglycerides, and platelet aggregation. A human study showed that eating two to three kiwifruits per day reduced triglyceride levels by 15% and reduced platelet aggregation response byActinidia deliciosa 18% compared to control.19 Multiple studies have shown that daily kiwi consumption improves not only triglyceride levels, but also the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol. One clinical trial studied male smokers who ate three kiwis per day for eight weeks. The patients had significantly reduced blood pressure and angiotensin-converting enzyme (ACE) activity (a component of the blood pressure-regulation process), especially those with hypertension. A number of in vitro studies support the claim that kiwifruit reduces platelet aggregation, but clinical trials are conflicting and more human studies are needed to confirm this effect.4 Antioxidant and Cytotoxic Properties The vitamin and phytochemical composition of kiwifruit give it powerful antioxidant properties. An in vivo study showed that kiwifruit juice ingestion increased plasma antioxidant capacity within 30 minutes and that these levels were sustained for up to 90 minutes. Though this was not a long-term study, this may have implications for kiwifruit’s ability to fight oxidative stress.3 Similar findings were established through two human studies in the United Kingdom, which showed that kiwifruit consumption improved antioxidant status of both the plasma and lymphocytes of participants. One of these studies also showed that kiwifruit seemed to stimulate DNA repair. A pilot study was performed to extrapolate on this possibility and the results showed that kiwi aided DNA repair for an average of 13 hours after ingestion.7 Though vitamin C is known for its antioxidant power, it also has a synergistic effect on iron absorption. In a study of young women with mild anemia (iron deficiency), participants who consumed two golden kiwifruits with an iron-fortified cereal daily had significantly improved iron levels compared to participants who ate the cereal with a banana. The vitamin C content, along with the carotenoids lutein and zeaxanthin present in kiwifruits, are likely responsible for this outcome.4 There is a great deal of investigation into the role of antioxidants and other phytochemicals in the prevention of cancerous cell growth, but despite kiwifruit’s history of use in traditional Chinese medicine, there are few clinical trials establishing the connection of the fruit and its constituents with cancer prevention or treatment. In vitro studies have shown that extracts of Actinidia species may be toxic to cancer cells. Additionally, mice studies have shown that kiwifruit juice inhibits growth of sarcoma cells.12 Another mouse study showed that catechin in the stems of A. arguta and the juice of A. deliciosa increased bone marrow proliferation, which may have implications for reducing the adverse effects of chemotherapy treatments. There has also been evidence suggesting that the prebiotic effect of fiber found in foods may change the bacteria in the colon, providing protection against colon cancer.3 Consumer Considerations Though it is poorly understood, there is an allergy risk associated with the fruits of Actinidia species. Allergic reactions can range from mild itching of the throat, mouth, and lips, and swelling to anaphylaxis, though it is more common for reactions to be mild. The more severe reactions typically occur in children.4 The prevalence of allergies to Actinidia fruits may vary geographically; in France, Finland, and Sweden, kiwifruit is one of the top ten most common allergens.16 Allergies to kiwifruit are often cross-reactive with other common allergens such as pollens, rye (Secale cereale, Poaceae), hazelnut (Corylus avellana, Betulaceae), chestnut (Castanea spp., Fagaceae), banana, and avocado (Persea americana, Lauraceae). Heat treatment and industrial homogenization have been shown to greatly reduce the allergic reactivity of green kiwi. These treatments are often performed on processed products like beverages and jams.20 Kiwifruit contains oxalate, which is from the salt of oxalic acid. Oxalates can cause oral irritation in some individuals, and they can be risky for individuals with a history of calcium oxalate-containing kidney stones. Oxalate in high concentrations can also reduce the bioavailability of calcium, magnesium, and iron in the body.3 Though kiwifruit contains more than 10 mg of oxalate per serving (enough to be considered high levels), it would require daily consumption of large quantities of kiwifruit for the levels of oxalates in the body to become dangerous. Additionally, oxalate content decreases during storage.16 Nutrient Profile21 Macronutrient Profile: (Per one fruit [approx. 69 grams]) 42 calories 0.8 g protein 10.1 g carbohydrate 0.4 g fat Secondary Metabolites: (Per one fruit [approx. 69 grams]) Excellent source of: Vitamin C: 64 mg (106.7% DV) Vitamin K: 27.8 mcg (34.8% DV) Good source of: Dietary Fiber: 2.1 g (8.4% DV) Potassium: 215 mg (6.1% DV) Vitamin E: 1 mg (5% DV) Also provides: Folate: 17 mcg (4.3% DV) Manganese: 0.07 mg (3.5% DV) Magnesium: 12 mg (3% DV) Calcium: 23 mg (2.3% DV) Phosphorus: 23 mg (2.3% DV) Vitamin B6: 0.04 mg (2% DV) Thiamin: 0.02 mg (1.3% DV) Niacin: 0.24 mg (1.2% DV) Riboflavin: 0.02 mg (1.2% DV) Vitamin A: 60 IU (1.2% DV) Iron: 0.2 mg (1.1% DV) DV = Daily Value as established by the US Food and Drug Administration, based on a 2,000-calorie diet. Recipe: Kiwi, Lemon, and Rosemary Shrub Courtesy of Jerry James Stone22 Ingredients: 1 1/2 pounds kiwifruit 2 slices of lemon 1 sprig of rosemary 1 cup sugar 1 cup champagne vinegar Directions: Peel and thinly slice the kiwifruit. Arrange a layer of kiwifruit in a quart-sized jar and sprinkle with sugar. Repeat the layering until all the sugar and fruit is in the jar. Seal and let stand for five hours. Add the lemon, rosemary, and vinegar to the jar. Seal and shake to combine and dissolve the sugar, then let stand for 24 hours. Strain the mixture through a sieve into a clean quart-sized jar. Seal and refrigerate. To serve, mix two tablespoons of the shrub with sparkling water in an ice-filled glass. References The National Geographic Society. Edible: An Illustrated Guide to the World’s Food Plants. Washington, DC: The National Geographic Society; 2008. Wojdyło A, Nowicka P, Oszmiański J, Golis T. Phytochemical compounds and biological effects of Actinidia fruits. J Funct Foods. 2017;30:194-202. doi:10.1016/j.jff.2017.01.018. Hunter DC, Skinner MA, Ferguson AR, Stevenson LM. Kiwifruit and health. In: Bioactive Foods in Promoting Health: Fruits and Vegetables. Auckland, New Zealand; 2010:565-580. doi:10.1016/B978-0-12-374628-3.00037-2. Stonehouse W, Gammon CS, Beck KL, Conlon C, von Hurst PR, Kruger R. Kiwifruit: our daily prescription for health. Can J Physiol Pharmacol. 2013;91(6):442-447. doi:10.1139/cjpp-2012-0303. van Wyk B-E. Food Plants of the World: An Illustrated Guide. Portland, OR: Timber Press; 2005. Murray M, Pizzorno J, Pizzorno L. The Encyclopedia of Healing Foods. New York, NY: Atria Books; 2005. Rush E, Ferguson LR, Cumin M, Thakur V, Karunasinghe N, Plank L. Kiwifruit consumption reduces DNA fragility: a randomized controlled pilot study in volunteers. Nutr Res. 2006;26(5):197-201. doi:10.1016/j.nutres.2006.05.002. Carr AC, Pullar JM, Moran S, Vissers MCM. Bioavailability of vitamin C from kiwifruit in non-smoking males: determination of “healthy” and “optimal” intakes. J Nutr Sci. 2012;1:e14. doi:10.1017/jns.2012.15. Weil A, Becker B. Facts about vitamin E. Weil website. August 2016. Available at: Accessed June 21, 2017. Ehrlich SD. Vitamin K. University of Maryland Medical Center website. July 16, 2013. Available at: Accessed June 22, 2017. Drummond L. Chapter three — The composition and nutritional value of kiwifruit. Adv Food Nutr Res. 2013;68:33-57. doi: Motohashi N, Shirataki Y, Kawase M, et al. Cancer prevention and therapy with kiwifruit in Chinese folklore medicine: A study of kiwifruit extracts. J Ethnopharmacol. 2002;81(3):357-364. doi:10.1016/S0378-8741(02)00125-3. Zhu WJ, Yu DH, Zhao M, et al. Antiangiogenic triterpenes isolated from Chinese herbal medicine Actinidia chinensis Planch. Anti-Cancer Agents Med Hist. 2013;13(2):195-198. doi:10.2174/187152013804711146. Hsu HY. Oriental Materia Medica: A Concise Guide. Long Beach, CA: Oriental Healing Arts Institute; 1986. Shu Q, Mendis De Silva U, Chen S, et al. Kiwifruit extract enhances markers of innate and acquired immunity in a murine model. Food Agric Immunol. 2008;19(2):149-161. doi:10.1080/09540100802117198. Singletary K. Kiwifruit. Nutr Today. 2012;47(3):133-147. doi:10.1097/NT.0b013e31825744bc. Parkar SG, Redgate EL, Wibisono R, Luo X, Koh ETH, Schröder R. Gut health benefits of kiwifruit pectins: Comparison with commercial functional polysaccharides. J Funct Foods. 2010;2(3):210-218. doi:10.1016/j.jff.2010.04.009. Edmunds SJ, Roy NC, Love DR, Laing WA. Kiwifruit extracts inhibit cytokine production by lipopolysaccharide-activated macrophages, and intestinal epithelial cells isolated from IL10 gene deficient mice. Cell Immunol. 2011;270(1):70-79. doi:10.1016/j.cellimm.2011.04.004. Park YS, Leontowicz H, Leontowicz M, et al. Comparison of the contents of bioactive compounds and the level of antioxidant activity in different kiwifruit cultivars. J Food Compos Anal. 2011;24(7):963-970. doi:10.1016/j.jfca.2010.08.010. Nishiyama I. Fruits of the Actinidia genus. Adv Food Nutr Res. 2007;52(6):293-324. doi:10.1016/S1043-4526(06)52006-6. Basic Report: 09148, Kiwifruit, green, raw. United States Department of Agriculture Agricultural Research Service website. May 2016. Available at: Accessed June 22, 2017. Stone JJ. Kiwi, lemon & rosemary shrub (drinking vinegar). Jerry James Stone website. December 4, 2013. Available at: Accessed June 22, 2017. [Editor’s note: The linked webpage contains profanity.]

Re: Natural Pomegranate Juice Demonstrates a Beneficial Effect on Systolic and Diastolic Blood Pressure and hs-CRP, while also Increasing Triglycerides and VLDL Cholesterol

Pomegranate (Punica granatum, Lythraceae) Metabolic Syndrome Cardiovascular Risk Factors Date: 09-15-2017 HC# 051757-576 Moazzen H, Alizadeh M. Effects of pomegranate juice on cardiovascular risk factors in patients with metabolic syndrome: a double-blinded, randomized crossover controlled trial. Plant Foods Hum Nutr. June 2017;72(2):126-133. Metabolic syndrome is the name for a group of risk factors (high blood pressure, increased blood levels of sugar and lipids, and excess body fat around the waist) that increase the development of cardiovascular disease. Foods high in polyphenols have high antioxidant and anti-inflammatory properties. Pomegranate (Punica granatum, Lythraceae) fruit juice may have cardiovascular benefits in relation to this issue. However, nutritionists are concerned with pomegranate's simultaneous effect on the rise of glycemic factors and sugar-dependent lipids; namely, triglycerides and very-low-density lipoprotein cholesterol (VLDL-C). The purpose of this randomized, double-blind, placebo-controlled, crossover study was to evaluate the effect of pomegranate juice on cardiometabolic indices and glycemic indices in patients with metabolic syndrome. Patients with metabolic syndrome (n = 32; aged 18-70 years) were recruited via advertisement in Shabestar, Iran. This study took place between December 2012 and January 2013. Included patients had ≥ 3 of 5 components of metabolic syndrome—namely, waist circumference > 88 cm for women and > 102 cm for men, serum triglycerides ≥ 150 mg/dL, high-density lipoprotein (HDL) cholesterol < 50 mg/dL for women and < 40 mg/dL for men, systolic blood pressure ≥ 135 mmHg or diastolic blood pressure ≥ 85 mmHg, and fasting plasma glucose concentration > 110 mg/dL. Excluded patients included those who were pregnant or breastfeeding; consumed alcohol; had systemic, inflammatory, hepatic, or kidney diseases; and were allergic to pomegranate juice or the pomegranate placebo. Patients were withdrawn from the data analysis if during the study they had any change of diet, any disease development, or had an increase in low-density lipoprotein (LDL) cholesterol where medications were needed. Patients were treated with either 500 mL pure pomegranate juice or placebo for 7 days, and, following a 7-day washout, they received the opposite treatment. Pomegranate juice was prepared by hand by the researchers. The arils were removed from Shiraz pomegranates and were manually squeezed to yield juice; no additives were used. The juice included anthocyanins, 100.46 mg/L; total phenolics, 69 mg/L; total flavonoids, 283.02; and antioxidant capacity (DPPHsc [2,2-diphenyl-1-picrylhydrazyl radical scavenging activity]), 69%. Food engineers created a placebo formula to resemble the pomegranate juice taste and color. The similarity of the placebo and pomegranate juice was confirmed by 3 expert testers. The placebo was void of any polyphenols. The patients were asked not to change their lifestyle, diet, or physical activity during the study. Food intake and physical activities were recorded in a diary for 3 days to ensure no changes were made during the study. Blood was drawn at baseline and after 7 days of treatment to measure high-sensitivity C-reactive protein (hs-CRP), fasting blood sugar, total cholesterol, blood insulin, triglycerides, HDL, LDL, and VLDL. Blood pressure also was measured. Thirty patients were included in the final analysis; 1 patient was withdrawn due to development of the flu and taking antibiotics, and 1 patient had emotional and psychological problems. There was no change in intake of energy, carbohydrates, protein, or fat. Triglyceride levels and VLDL were significantly higher after pomegranate juice than after the placebo (P = 0.025 and P = 0.016, respectively). Blood hs‑CRP was significantly lower after pomegranate juice compared with baseline (P = 0.028) and placebo (P = 0.018). After pomegranate juice consumption, systolic and diastolic blood pressure significantly decreased compared to baseline and placebo (P < 0.001 for all). After placebo, systolic blood pressure significantly decreased compared to baseline (P = 0.007). The authors conclude that 500 mL/day of natural pomegranate juice had a beneficial effect on systolic and diastolic blood pressure and hs-CRP, despite increasing triglyceride and VLDL levels. Other studies report no effect of pomegranate juice on hs-CRP, while one reported a beneficial effect in overweight and obese individuals. The authors hypothesize that the difference between their findings and other reports can be attributed to the high daily dose of pomegranate juice in this study and the variety (Shiraz) of pomegranate used. It is not surprising that the increase in triglycerides was accompanied by an increase in VLDL because VLDL transports triglycerides. A meta-analysis concluded that the significant increase of triglycerides could disappear with long-term use.1 The authors state that, "This study showed that nutritionists, at least in the short-term, were right in being concerned because consuming pomegranate juice, in addition to having beneficial effects on blood pressure and inflammatory indices, has harmful effects on triglyceride and VLDL-C which is due to its high level of fructose." Long-term studies in a larger population are needed to confirm these short-term results. The authors declare that they have no conflict of interests. The study was funded by Urmia University of Medical Sciences; Urmia, Iran. —Heather S. Oliff, PhD Reference 1Sahebkar A, Simental-Mendía LE, Giorgini P, Ferri C, Grassi D. Lipid profile changes after pomegranate consumption: a systematic review and meta-analysis of randomized controlled trials. Phytomedicine. 2016;23(11):1103-1112.

Re: Review of Studies of Grape Products Documents Bioactivities that May Reduce Risk of Cardiovascular Disease

Grape (Vitis vinifera, Vitaceae) Polyphenols Cardiovascular Disease Diabetes Date: 09-15-2017 HC# 021742-576 Rasines-Perea Z, Teissedre P-L. Grape polyphenols' effects in human cardiovascular diseases and diabetes. Molecules. January 1, 2017;22(1):68. doi: 10.3390/molecules22010068. Polyphenols, the most abundant secondary metabolites in plants, include flavonoids and non-flavonoids. Dietary intake of polyphenols varies greatly and is difficult to quantify. Polyphenols are poorly characterized in foods and their quantity may vary depending on factors including plant genetics and preparation and storage methods. Epidemiological and clinical studies report that moderate consumption of alcoholic drinks, including wine and juice from grapes (Vitis vinifera, Vitaceae) and from Concord grapes (V. labrusca), affects antioxidant capacity, lipid profiles, and blood coagulation and may reduce incidence of cardiovascular disease (CVD) and total mortality. Type 2 diabetes is often associated with CVD and heart failure, sharing many risk factors. Several studies of grapes and their components, mainly polyphenols and especially resveratrol (RES), have examined the relationship between grape consumption and CVD. The authors review the published benefits of grape polyphenols related to CVD and diabetes but do not describe their search strategy. High blood pressure (BP) is the largest proximal risk factor for CVD; depending upon age, systolic BP (SBP) that is lowered by only 2 mm Hg can be associated with meaningful reductions in CVD mortality. Antihypertensives were the most prescribed drugs in the United States in 2012 and 2013, but hypertension can also be reduced with diet. Studies with grapes that included BP measurements have mostly been conducted in cohorts with prehypertensive average baseline BP, but some have included subjects with metabolic syndrome, with above-average vascular risk, and/or mild to moderate hypertension. Decreases in SBP have been reported with grape seed extract (GSE) supplementation and some report similar drops in diastolic BP (DBP). A meta-analysis of nine randomized controlled trials (RCTs) found that GSE significantly lowered SBP by −1.54 mm Hg (P=0.02) but had no significant effect on DBP. However, some individual RCTs have reported far larger effects. One RCT with a dosage of 150 mg, the lowest of all the RCTs, significantly dropped SBP by −11 mm Hg and DBP by −7 mm Hg compared to placebo. This study used a uniquely processed GSE with a patented composition called MegaNatural®-BP (Polyphenolics; Madera, California). One cited RCT found decreases in SBP and DBP in both the GSE and placebo groups, with a larger decrease in the former. Some trials in people with normal or near-normal BP found no significant BP changes. More RCTs are needed to determine the effect of grape polyphenols on BP, but they show the most promise in those with higher BP. High plasma levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are risk factors for CVD. Polyphenols affect hepatic cholesterol and lipoprotein metabolism by reducing cholesterol absorption and delivery of cholesterol to the liver, thus reducing plasma cholesterol. Polyphenols also affect apolipoproteins (apo) A and B, modify very-low-density lipoprotein (VLDL) particles, and reduce plasma triglyceride (TG) levels, possibly by boosting lipoprotein lipase (LPL) activity. Studies report reductions in total cholesterol (TC), LDL-C, and apo B-100, as well as higher apo A-1 and HDL-C, in healthy individuals and patients undergoing hemodialysis after 14 days of supplementation with 100 mL/d concentrated Bobal* grape juice. Studies with Concord grape juice found increases in TG levels and no changes in TC, HDL-C, or LDL-C. Other studies report varying results with different products and study populations. A study using a GSE product (MegaNatural-Gold; Polyphenolics) found TC, LDL-C, and HDL-C significantly decreased (TC and LDL-C, P<0.01; HDL-C, P<0.05) after three weeks in eight patients with hypercholesterolemia and remained unchanged in nine subjects with normal lipid levels. A crossover RCT with 45 overweight and slightly obese men and women found no difference in HDL-C or LDL-C with 150 mg/d RES or placebo for four weeks. In a double-blind RCT with 40 post-infarction patients, 10 mg/d RES for three months resulted in improvements in endothelial function measured by flow-mediated vasodilation and LDL-C levels (both P<0.05). Grape polyphenols slow LDL oxidation and thus atherosclerosis. Two studies in patients undergoing hemodialysis who consumed 100 mL/d concentrated Bobal grape juice for 14 days found decreases in oxidized LDL (ox-LDL) of 35% and 65%, respectively. Studies using Concord grape juice have reported increases in LDL velocity and, in one case, a 9% reduction in LDL oxidation. In one study, Concord grape juice significantly reduced thiobarbituric acid reactive substances (TBARS) compared to water. One study of GSE found significantly reduced TBARS levels and prolonged lag time for LDL oxidation; another, no change in ox-LDL after supplementation with 1000 mg/d GSE for six weeks. A six-month, triple-blinded RCT of RES-enriched GSE supplementation in 75 patients for primary prevention of CVD found decreased LDL-C (P=0.04), apo B (P=0.014), and ox-LDL (P=0.001); RES was said to be necessary for these effects. Reduced superoxide anion production, involved in formation of ox-LDL, has been found for neutrophils and platelets in different studies of purple grape juice and Concord grape juice. Regarding F2-isoprostanes, an indicator of oxidative stress, conflicting results are reported, with some studies finding decreased levels and others no change or even increased levels. Two studies of the effect of grape supplementation on DNA damage as a marker of oxidative stress found significant decreases in lymphocyte DNA damage for different products in different patient cohorts. Four studies of platelet activation and one of atrial fibrillation suggest more CVD-related benefits of grapes. In one of the former, white grape juice inhibited platelet aggregation more than red grape juice. Six studies reported findings indicating the potential role of grape polyphenols, particularly anthocyanins, flavan-3-ols, and RES, in reducing risk of diabetes. In one, both alcoholic and dealcoholized red wine significantly improved insulin levels over baseline; gin (often flavored with juniper [Juniperus communis, Cupressaceae] berry) did not. Larger, better-quality studies are needed and justified. —Mariann Garner-Wizard *The Bobal variety of V. vinifera comes from the Utiel-Requena region, Valencia, Spain.

Tuesday, 19 September 2017

Doctoral Research Fellow in Bioethics connected to the project "Epigenetics and bioethics of human embryonic development" A Doctoral Research Fellowship in Bioethics is open at the Department of Philosophy, Classics, History of Art and Ideas, University of Oslo

The University of Oslo is Norway’s oldest and highest ranked educational and research institution, with 28 000 students and 7000 employees. With its broad range of academic disciplines and internationally recognised research communities, UiO is an important contributor to society. The Department embraces four disciplines: Philosophy, Classical Languages (Greek and Latin), History of Ideas and Art History. The Department is also responsible for the introductory philosophy courses, obligatory for all students attending study programmes at the University of Oslo. The Department has about 140 employees. . Job description The post will be associated with the convergence project “Epigenetics and bioethics of human embryonic development” funded by University of Oslo Life Sciences. The person appointed will be supervised by Anna Smajdor, who is leading the ethics component of the project. The PhD position is open for proposals that investigate the ethical implications of greater scientific knowledge and control over human embryos in research and fertility treatment. As our understanding of embryonic development increases, there are more opportunities to make judgments as to which embryos are ‘best’ for implantation. Not only this, but it is becoming possible to effect changes to embryos, either through altering the environment in which they are stored, or through intervening on them directly. The successful candidate will explore the ethical significance of these new aspects of control. The PhD student will be affiliated with the Faculty's organized research training. The academic work is to result in a doctoral thesis that will be defended at the Faculty with a view to obtaining the degree of PhD. The successful candidate is expected to join the existing research milieu and contribute to its development. Read more about the doctoral degree. The appointment is for a duration of three years. All PhD Candidates who submit their doctoral dissertation for assessment with a written recommendation from their supervisor within 3 years or 3 ½ years after the start of their PhD position, will be offered, respectively, a 12 or 6 month Completion Grant. Qualification requirements A Master's Degree or equivalent in philosophy or other relevant discipline. The Master's Degree must have been obtained by the time of application. A project description relevant to the ethics of embryo selection. In assessing the applications, special emphasis will be placed on: The bioethical merit, relevance and innovation of the proposed project The applicant's estimated academic and personal ability to complete the project within the time frame Good collaborative skills and willingness to work with scientists and social scientists Personal suitability and motivation for the position We offer salary level NOK 436 900 – 490 900, depending on qualifications a professionally stimulating working environment attractive welfare benefits How to apply Applicants must submit the following attachments with the electronic application, preferably in pdf format: Application letter describing the applicant’s motivation for the position Curriculum Vitae (complete list of education, positions, teaching experience, administrative experience and other qualifying activities, including a complete list of publications) Transcript of records of the applicant’s Master's degree. Applicants with education from a foreign university are advised to attach an explanation of their university's grading system Project description, including a detailed progress plan for the project (3-5 pages, see Template for project descriptions) List of reference persons: 2-3 references (name, relation to candidate, e-mail and phone number) The application with attachments must be delivered in our electronic recruiting system, please follow the link “apply for this job”. Please submit all documents in English, to the extent possible. Short-listed candidates may be invited for an interview at the University of Oslo or via Skype. Formal regulations Please see the Guidelines for the application assessment process and appointments to research fellowships. Following the Freedom of Information Act (Offentleglova) § 25, Chapter 2, demographic information about the applicant may be used in the public list of applicants even if the applicant opts out from the entry in the public application list. The University of Oslo has an Acquisition of Rights Agreement for the purpose of securing rights to intellectual property created by its employees, including research results. The University of Oslo aims to achieve a balanced gender composition in the workforce and to recruit people with ethnic minority backgrounds. Deadline: 1 November 2017 Contact persons For questions about the position: Associate professor Anna Smajdor For questions about the recruitment process: HR-Officer Julie Tøllefsen