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https://www.readbyqxmd.com/read/28333866/prevention-of-gastrointestinal-side-effects-in-paediatric-oncology-what-are-the-guidelines
#1
Karis K F Cheng
PURPOSE OF REVIEW: Gastrointestinal side-effects, particularly with regard to alimentary tract mucositis and chemotherapy-induced nausea and vomiting (CINV), continue to be frequent and debilitating symptomatic conditions among children and adolescents receiving cytotoxic cancer therapy. Further avenues of progress for mucositis and CINV prevention in paediatric oncology setting are warranted. RECENT FINDINGS: The current article reviews the major guidelines and literature published in 2016 pertaining to the prevention of mucositis and CINV...
March 22, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28316078/5-ht3a-driven-gfp-delineates-gustatory-fibers-innervating-sour-responsive-taste-cells-a-labeled-line-for-sour-taste
#2
J M Stratford, E D Larson, R Yang, E Salcedo, T E Finger
Taste buds contain multiple cell types with each type expressing receptors and transduction components for a subset of taste qualities. The sour sensing cells, Type III cells, release serotonin (5-HT) in response to the presence of sour (acidic) tastants and this released 5-HT activates 5-HT3 receptors on the gustatory nerves. We show here, using 5-HT3A GFP mice, that 5-HT3 -expressing nerve fibers preferentially contact and receive synaptic contact from Type III taste cells. Further, these 5-HT3 -expressing nerve fibers terminate in a restricted central-lateral portion of the nucleus of the solitary tract (nTS) - the same area that shows increased c-Fos expression upon presentation of a sour tastant (30 mM citric acid)...
March 17, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28291778/efficacy-and-safety-of-5-hydroxytryptamine-3-receptor-antagonists-in-irritable-bowel-syndrome-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#3
Yongping Zheng, Ting Yu, Yurong Tang, Wenjie Xiong, Xiaoxue Shen, Ling Jiang, Lin Lin
AIM: We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D). METHODS: We searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT3 receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation...
2017: PloS One
https://www.readbyqxmd.com/read/28280410/lamotrigine-an-antiepileptic-drug-inhibits-5-ht3-receptor-currents-in-ncb-20-neuroblastoma-cells
#4
Ki Jung Kim, Seung Hyun Jeun, Ki-Wug Sung
Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)3 receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC50 value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28272863/serotonin-transporter-independent-actions-of-the-antidepressant-vortioxetine-as-revealed-using-the-sert-met172-mouse
#5
Alex G Nackenoff, Linda D Simmler, Nicole L Baganz, Alan L Pehrson, Connie Sánchez, Randy D Blakely
Selective serotonin (5-HT, SERT) reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression. However, they have delayed efficacy and can induce side-effects that can encourage discontinuation. Recently, agents have been developed, including vortioxetine (Trintellix), that augment SERT blockade with interactions at other targets. At therapeutic doses, vortioxetine interacts with SERT as well as 5-HT1A, 5-HT1B, 5-HT3, and 5-HT7 receptors. We assessed the SERT-dependency of vortioxetine action using the SERT Met172 mouse model, which disrupts high-affinity interactions of many antidepressants with the transporter...
March 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28270854/antiemetic-and-myeloprotective-effects-of-rhus-verniciflua-stoke-in-a-cisplatin-induced-rat-model
#6
Hyo-Seon Kim, Hyeong-Geug Kim, Hwi-Jin Im, Jin-Seok Lee, Sung-Bae Lee, Won-Yong Kim, Hye-Won Lee, Sam-Keun Lee, Chang Kyu Byun, Chang-Gue Son
Rhus verniciflua Stoke has been commonly used in traditional medicine to treat gastrointestinal (GI) dysfunction diseases. In order to investigate pharmacological properties of Rhus verniciflua Stoke water extract (RVX) on cisplatin-induced amnesia, RVX (0, 25, 50, or 100 mg/kg) was orally administrated for five consecutive days after a single intraperitoneal injection of cisplatin (6 mg/kg) to SD rat. Cisplatin injection significantly increased the kaolin intake (emesis) but reduced the normal diet intake (anorexia) whereas the RVX treatment significantly improved these abnormal diet behaviors at both the acute and delayed phase...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28259598/tropisetron-sensitizes-%C3%AE-7-containing-nicotinic-receptors-to-low-levels-of-acetylcholine-in%C3%A2-vitro-and-improves-memory-related-task-performance-in-young-and-aged-animals
#7
Patrick M Callahan, Daniel Bertrand, Sonia Bertrand, Marc R Plagenhoef, Alvin V Terry
Tropisetron, a 5-HT3 receptor antagonist commonly prescribed for chemotherapy-induced nausea and vomiting also exhibits high affinity, partial agonist activity at α7 nicotinic acetylcholine receptors (α7 nAChRs). α7 nAChRs are considered viable therapeutic targets for neuropsychiatric disorders such as Alzheimer's disease (AD). Here we further explored the nAChR pharmacology of tropisetron to include the homomeric α7 nAChR and recently characterized heteromeric α7β2 nAChR (1:10 ratio) and we evaluated its cognitive effects in young and aged animals...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28245760/peripheral-corticotropin-releasing-factor-signaling-inhibits-gastric-emptying-mechanisms-of-action-and-role-in-stress-related-gastric-alterations-of-motor-function
#8
József Czimmer, Yvette Taché
The activation of corticotrophin releasing-factor (CRF) receptors in the brain is well established to coordinate the endocrine, behavioral, autonomic and visceral responses to stress. In addition, CRF receptors are also expressed within the gut where they exert biological actions and play a role in modulating stress-related gastrointestinal function. In particular, peripheral injection of CRF and related peptides, urocortin 1, 2 or 3 inhibit gastric emptying (GE) and alters fasted and fed pattern of gastroduodenal motility in several experimental species...
February 28, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28243846/protective-effect-of-tropisetron-on-high-glucose-induced-apoptosis-and-oxidative-stress-in-pc12-cells-roles-of-jnk-p38-mapks-and-mitochondria-pathway
#9
Azadeh Aminzadeh
Tropisetron, a selective 5-HT3 receptor (5-HT3R) antagonist, is widely used to counteract chemotherapy-induced emesis. There is growing interest concerning the beneficial effects of tropisetron on the treatment of several diseases. This study was carried out to examine effects of tropisetron on high glucose (HG) induced apoptosis in PC12 cells as a suitable culture model for studying neuronal functions. Apoptosis was induced by HG, and cells were treated with HG in the absence and presence of tropisetron for varying periods of time...
February 27, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28238069/novel-5-ht3-receptor-antagonist-qcm-4-attenuates-depressive-like-phenotype-associated-with-obesity-in-high-fat-diet-fed-mice
#10
Yeshwant Kurhe, R Mahesh, Thangaraj Devadoss
RATIONALE: Depression associated with obesity remains an interesting area to study the biological mechanisms and novel therapeutic intervention. OBJECTIVES: The present study investigates the effect of a novel 5-HT3 receptor antagonist 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4) on several pathogenic markers of depression associated with obesity such as plasma insulin resistance, hippocampal cyclic adenosine monophosphate (cAMP), brain-derived neurotrophic factor (BDNF), serotonin (5-HT) concentrations, hippocampal neuronal damage, and p53 protein expression in high-fat-diet (HFD)-fed mice...
February 25, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28237803/serotonin-mediated-modulation-of-acetylcholine-induced-intracellular-calcium-responses-in-chromaffin-cells-isolated-from-the-rat-adrenal-medulla
#11
Takuya Yokoyama, Yoshio Yamamoto, Tomoyuki Saino
We examined serotonin (5-HT)-mediated modulation of acetylcholine (ACh)-induced intracellular Ca(2+) ([Ca(2+)]i) responses in rat adrenal chromaffin cells using calcium imaging. 5-HT did not induce any [Ca(2+)]i response in clustered chromaffin cells. However, the magnitude of ACh-induced [Ca(2+)]i increases in the same specimens was inhibited in the presence of 5-HT. ACh-induced [Ca(2+)]i increases in chromaffin cells were also inhibited by the 5-HT1A receptor agonist, 8-hydroxy-2-(dipropylamino) tetralin hydrobromide, but were not changed by the 5-HT1B, 5-HT2, or 5-HT3 receptor agonists, CP93129, α-methyl-5-HT, or 1-(m-chlorophenyl) biguanide, respectively...
February 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28235999/concise-review-of-the-management-of-iatrogenic-emesis-using-cannabinoids-emphasis-on-nabilone-for-chemotherapy-induced-nausea-and-vomiting
#12
REVIEW
Joseph V Pergolizzi, Robert Taylor, Jo Ann LeQuang, Gianpietro Zampogna, Robert B Raffa
Chemotherapy-induced nausea and vomiting (CINV) is a prevalent, distressing, and burdensome side effect of cancer chemotherapy. It is estimated to affect the majority of patients receiving certain anti-cancer drug regimens and can be treatment-limiting, even for life-saving medications. Despite seemingly numerous options, such as antimuscarinic anticholinergics, antihistamines, 5-HT3 receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists, preventative therapies are often inadequately effective, particularly for "delayed CINV"-leaving an important unmet clinical need...
March 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28216898/depolarizing-effects-of-daikenchuto-on-interstitial-cells-of-cajal-from-mouse-small-intestine
#13
Hyungwoo Kim, Hyun Jung Kim, Dongki Yang, Myeong Ho Jung, Byung Joo Kim
BACKGROUND: Daikenchuto (DKT; TJ-100, TU-100), a traditional herbal medicineis used in modern medicine to treat gastrointestinal (GI) functional disorders. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the GI tract and play important roles in the regulation of GI motility. OBJECTIVE: The objective of this study was to investigate the effects of DKT on the pacemaker potentials (PPs) of cultured ICCs from murine small intestine. MATERIALS AND METHODS: Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28211304/granisetron-and-carvedilol-can-protect-experimental-rats-againstadjuvant-induced-arthritis
#14
Yasmin Moustafa Ahmed, Basim Anwar Shehata Messiha, Ali Ahmed Abo-Saif
CONTEXT: Rheumatoid arthritis (RA), a disabling autoimmune disorder of the joints as well as other organs, affects about 1% of population. Unfortunately, all current treatments of RA cause severe gastrointestinal, renal and other complications. OBJECTIVE: We aimed to evaluate the possible antiarthritic effects of a serotonin 5-HT3 receptor blocker, granisetron, and a nonselective adrenergic receptor blocker, carvedilol, on complete Freund's adjuvant-induced RA in adult female albino rats...
April 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28156640/efficacy-of-rolapitant-for-prevention-of-chemotherapy-induced-nausea-and-vomiting-cinv-in-patients-with-gastrointestinal-and-colorectal-cancers
#15
Karin Jordan, Bernardo Leon Rapoport, Ian D Schnadig, Martin Chasen, Sujata Arora, Daniel Powers, Lee Steven Schwartzberg
222 Background: Rolapitant (VARUBI) is a selective, long-acting neurokinin-1 receptor antagonist (RA) for the prevention of CINV. Rolapitant effectively prevented CINV in phase 3 trials of patients (pts) receiving highly or moderately emetogenic chemotherapy (HEC, MEC). While MEC and HEC regimens are commonly used to treat pts with gastrointestinal and colorectal cancers (GI/CRC), very few studies have evaluated the effectiveness of a neurokinin-1 RA regimen in these pts. We assessed the incidence of CINV and efficacy of rolapitant in a subset of pts with GI/CRC...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152932/national-comprehensive-cancer-network-petitions-submissions-and-outcomes
#16
Dinah Faith Huff, William J Hrushesky, Charles Lee Bennett, Kevin Knopf, Michael Baum
248 Background: The National Comprehensive Cancer Network (NCCN) invites petitions to its scientific panels. Most ( > 95%) are from the pharmaceutical industry lobbying to include their products in the NCCN Guidelines. Rarely, physicians request scientific scrutiny of the guidelines. We report the experience of Oncology Analytics (OA) with petition submissions and the possible impact on guidelines. METHODS: From 2011-2015, OA made 7 petitions to NCCN. The content of each was tracked into subsequent NCCN Guidelines to ascertain whether any changes resulted...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152708/influencing-antiemetic-prescribing-practices-and-funding-changes-through-evidence-based-guidelines
#17
Michael Wan, Aliya Pardhan, Erin Redwood, Andrea Crespo, Nita Lakhani, Leonard Kaizer
31 Background: In 2013 Cancer Care Ontario released updated antiemetic recommendations supporting the use of aprepitant-based combinations as 1(st) line therapy for highly emetogenic and 2(nd) line therapy for moderately emetogenic chemotherapy and discouraging the prolonged use of 5-HT3 antagonists. In 2014 changes were made in the Ontario drug formulary to align public funding to those recommendations. The impact of the changes in guidance and public funding on prescribing practices are now being analyzed...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152579/5htr3a-driven-gfp-labels-immature-olfactory-sensory-neurons
#18
Thomas E Finger, Dianna L Bartel, Nicole Shultz, Noah B Goodson, Charles A Greer
The ionotropic serotonin receptor, 5-HT3 , is expressed by many developing neurons within the central nervous system. Since the olfactory epithelium continues to generate new olfactory sensory neurons (OSNs) throughout life, we investigated the possibility that 5-HT3 is expressed in the adult epithelium. Using a transgenic mouse in which the promoter for the 5-HT3a subunit drives expression of green fluorescent protein (GFP), we assessed the expression of this marker in the olfactory epithelium of adult mice...
February 2, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28137449/the-binding-orientations-of-structurally-related-ligands-can-differ-a-cautionary-note
#19
Marc-David Ruepp, Hao Wei, Michele Leuenberger, Martin Lochner, Andrew J Thompson
Crystal structures can identify ligand-receptor interactions and assist the development of novel therapeutics, but experimental challenges sometimes necessitate the use of homologous proteins. Tropisetron is an orthosteric ligand at both 5-HT3 and α7 nACh receptors and its binding orientation has been determined in the structural homologue AChBP (pdbid: 2WNC). Co-crystallisation with a structurally-related ligand, granisetron, reveals an almost identical orientation (pdbid; 2YME). However, there is a >1000-fold difference in the affinity of tropisetron at 5-HT3 versus α7 nACh receptors, and α7 nACh receptors do not bind granisetron...
January 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28115218/contrasting-effects-of-5-ht3-receptor-stimulation-of-the-nucleus-accumbens-or-ventral-tegmentum-on-food-intake-in-the-rat
#20
Wayne E Pratt, Peagan Lin, Zachary Pierce-Messick, Adeolu O Ilesanmi, Kara A Clissold
Although serotonin (5-HT) signaling is known to regulate food intake and energy homeostasis, the roles of the 5-HT3 receptor in feeding processes have been elusive. 5-HT3 receptors are found throughout mesolimbic circuitry that promote feeding not only in response to hunger, but also to the palatable and rewarding properties of food. These experiments examined if stimulation or blockade of the 5-HT3 receptor of the nucleus accumbens (NAcc) or ventral tegmentum affected food intake in the rat in response to hunger or the presence of a palatable diet...
April 14, 2017: Behavioural Brain Research
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