Clot activators and anticoagulant additives for blood collection. A critical review on behalf of COLABIOCLI WG-PRE-LATAM.

In the clinical laboratory, knowledge of and the correct use of clot activators and anticoagulant additives are critical to preserve and maintain samples in optimal conditions prior to analysis. In 2017, the Latin America Confederation of Clinical Biochemistry (COLABIOCLI) commissioned the Latin American Working Group for Preanalytical Phase (WG-PRE-LATAM) to study preanalytical variability and establish guidelines for preanalytical procedures to be applied by clinical laboratories and health care professionals. The aim of this critical review, on behalf of COLABIOCLI WG-PRE-LATAM, is to provide information to understand the mechanisms of the interactions and reactions that occur between blood and clot activators and anticoagulant additives inside evacuated tubes used for laboratory testing. Clot activators - glass, silica, kaolin, bentonite, and diatomaceous earth - work by surface dependent mechanism whereas extrinsic biomolecules - thrombin, snake venoms, ellagic acid, and thromboplastin - start in vitro coagulation when added to blood. Few manufacturers of evacuated tubes state the type and concentration of clot activators used in their products. With respect to anticoagulant additives, sodium citrate and oxalate complex free calcium and ethylenediaminetetraacetic acid chelates calcium. Heparin potentiates antithrombin and hirudin binds to active thrombin, inactivating the thrombin irreversibly. Blood collection tubes have improved continually over the years, from the glass tubes containing clot activators or anticoagulant additives that were prepared by laboratory personnel to the current standardized evacuated systems that permit more precise blood/additive ratios. Each clot activator and anticoagulant additive demonstrates specific functionality, and both manufacturers of tubes and laboratory professional strive to provide suitable interference-free sample matrices for laboratory testing. Both manufacturers of in vitro diagnostic devices and laboratory professionals need to understand all aspects of venous blood sampling so that they do not underestimate the impact of tube additives on laboratory testing.

(Bio)electrochemical ammonia recovery: progress and perspectives.

In recent years, (bio)electrochemical systems (B)ES have emerged as an energy efficient alternative for the recovery of TAN (total ammonia nitrogen, including ammonia and ammonium) from wastewater. In these systems, TAN is removed or concentrated from the wastewater under the influence of an electrical current and transported to the cathode. Subsequently, it can be removed or recovered through stripping, chemisorption, or forward osmosis. A crucial parameter that determines the energy required to recover TAN is the load ratio: the ratio between TAN loading and applied current. For electrochemical TAN recovery, an energy input is required, while in bioelectrochemical recovery, electric energy can be recovered together with TAN. Bioelectrochemical recovery relies on the microbial oxidation of COD for the production of electrons, which drives TAN transport. Here, the state-of-the-art of (bio)electrochemical TAN recovery is described, the performance of (B)ES for TAN recovery is analyzed, the potential of different wastewaters for BES-based TAN recovery is evaluated, the microorganisms found on bioanodes that treat wastewater high in TAN are reported, and the toxic effect of the typical conditions in such systems (e.g., high pH, TAN, and salt concentrations) are described. For future application, toxicity effects for electrochemically active bacteria need better understanding, and the technologies need to be demonstrated on larger scale.

Analytic Hierarchy Process to Define the Most Important Factors and Related Technologies for Empowering Elderly People in Taking an Active Role in their Health.

Successful management of health conditions in older population is determined by strategic involvement of a professional team of careers and by empowering patients and their caregivers to take over a central role and responsibility in the daily management of condition. Identifying, structuring and ranking the most important needs related to these aspects could pave the way for improved strategies in designing systems and technological solutions supporting user empowerment. This paper presents the preliminary results of a study aiming to elicit these needs. Healthcare professionals, working together in the European and Innovation Partnership on Active and Healthy Ageing (EIP-AHA) initiative, have defined a set of needs and factors that have been organized in two hierarchies around the concepts of patient activation and proactive and prepared care team, defined in the Chronic Care Model. The two hierarchies have been mapped, by a team of experts in computer science, with technologies and solutions that could facilitate the achievement of the identified needs.

Studies of the Room-Temperature Multiferroic Pb(Fe0.5Ta0.5)0.4(Zr0.53Ti0.47)0.6O3: Resonant Ultrasound Spectroscopy, Dielectric, and Magnetic Phenomena.

Recently, lead iron tantalate/lead zirconium titanate (PZTFT) was demonstrated to possess large, but unreliable, magnetoelectric coupling at room temperature. Such large coupling would be desirable for device applications but reproducibility would also be critical. To better understand the coupling, the properties of all 3 ferroic order parameters, elastic, electric, and magnetic, believed to be present in the material across a range of temperatures, are investigated. In high temperature elastic data, an anomaly is observed at the orthorhombic mm2 to tetragonal 4mm transition, Tot = 475 K, and a softening trend is observed as the temperature is increased toward 1300 K, where the material is known to become cubic. Thermal degradation makes it impossible to measure elastic behavior up to this temperature, however. In the low temperature region, there are elastic anomalies near ≈40 K and in the range 160-245 K. The former is interpreted as being due to a magnetic ordering transition and the latter is interpreted as a hysteretic regime of mixed rhombohedral and orthorhombic structures. Electrical and magnetic data collected below room temperature show anomalies at remarkably similar temperature ranges to the elastic data. These observations are used to suggest that the three order parameters in PZTFT are strongly coupled.

Hepatic and adipocyte cells respond differentially to iron overload, hypoxic and inflammatory challenge.

Adipose tissue secretes numerous pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α that can lead to insulin resistance (IR). In the liver, both IL-6 and TNF-α induce IR by inhibiting phosphorylation or ubiquitination of IRS1. In IR development, Fe is a risk factor in type-2 diabetes development. We studied the expression of genes related to inflammation, hypoxia, and mitochondrial function in hepatic (HepG2) and adipose (3T3-L1) cells. HepG2 and 3T3-L1 cells were incubated with 20 µM Fe, 40 µM Fe, or 40 µM Fe/20 mM glucose for 7 days and then challenged with 20 ng/ml IL-6 and/or 100 µM CoCl(2) for 20 h. We measured intracellular Fe levels and the relative expression of hepcidin, NF-κB, IL-6, TNF-α, hypoxia inducible factor 1α (HIF-1α), and mitofusin 2 (Mfn-2) mRNA using qRT-PCR. The intracellular Fe concentration in HepG2 cells did not change with 20 or 40 µM Fe. However, levels were decreased with Fe/glucose and IL-6 and/or CoCl(2). 3T3-L1 cells showed an increase in intracellular Fe with high Fe plus either IL-6 or CoCl(2). HepG2 cells incubated with 40 µM Fe alone or Fe/glucose and challenged with IL-6 and/or CoCl(2) showed increased IL-6, NF-κB, and TNF-α mRNA expression and decreased mRNA expression of Mfn-2 in all experimental conditions. 3T3-L1 cells incubated with 40 µM Fe alone or Fe/glucose and challenged with IL-6 showed increased NF-κB mRNA expression and decreased Mfn-2 expression in all experimental conditions. Thus, high Fe, inflammation, and hypoxia trigger the expression of genes related to inflammation and Fe metabolism in HepG2 cells, in 3T3-L1 cells the same stimuli increased NF-kB and hepcidin expression.

Exchange coupling and exchange bias in La0.7Sr0.3MnO3-SrRuO3 superlattices.

La(0.7)Sr(0.3)MnO(3)-SrRuO(3) superlattices with and without nanometrically thin SrTiO(3), BaTiO(3) and Ba(0.7)Sr(0.3)TiO(3) interlayers were grown by pulsed laser deposition. Transmission electron microscopy studies showed coherent growth of La(0.7)Sr(0.3)MnO(3), SrRuO(3) and SrTiO(3) layers with atomically sharp interfaces, even if individual layers were as thin as one or two unit cells. In contrast, misfit dislocations and unit cell high interfacial steps were observed at the interfaces between BaTiO(3) and one of the ferromagnetic layers. The presence of the interlayers as well as these extended defects had a significant influence on the magnetic properties of the superlattices, especially on the antiferromagnetic interlayer exchange coupling between the La(0.7)Sr(0.3)MnO(3) and SrRuO(3) layers and the exchange biasing. Surprisingly, exchange biasing was found to increase with decreasing strength of the antiferromagnetic interlayer exchange coupling. This was explained by different magnetization reversal mechanisms acting in the regimes of strong and weak interlayer exchange coupling.

Transepithelial heme-iron transport: effect of heme oxygenase overexpression.

BACKGROUND: Heme iron is found in the diet mainly in the form of hemoglobin and myoglobin. It is known that heme iron (heme-Fe) and inorganic iron are absorbed differently. Intracellularly, heme oxygenase-1 (HO1) participates in the cleavage of the heme ring producing biliverdin, CO and ferrous iron. Iron released from heme becomes part of labile iron pool, and it can be stored in ferritin or released through the basolateral membrane. The mechanism by which heme-Fe is metabolized within cells is not completely understood. OBJECTIVE: This study focused on the uptake and transport of heme iron and on the role of heme oxygenase-1 on heme iron metabolism. DESIGN: Caco-2 cells were incubated with different concentrations of heme-Fe. A full-length heme oxygenase-1 cDNA was expressed in Caco-2 cells and intracellular iron and heme-Fe content, heme uptake, heme and iron transport and heme oxygenase-1 immunolocalization were assessed in these cells. RESULTS: Heme-Fe was bioavailable and induced an intracellular increase in iron, ferritin and HO1 levels and a decrease in DMT1 expression. In cells overexpressing HO1, heme-Fe uptake and transepithelial Fe transport was higher than in controls. Most heme-Fe was metabolized to free iron, most of which was found mainly in the basolateral chamber. However, there is a fraction of heme that is delivered intact to the basolateral side. In a high heme-Fe condition, HO1 is found near the plasma membrane. CONCLUSIONS: These results suggest that heme oxygenase-1 catabolizes most of the heme-Fe and favors iron influx and efflux in intestinal cells.

A mindfulness training program based on brief practices (M-PBI) to reduce stress in the workplace: a randomised controlled pilot study.

Work stress is a major contributor to absenteeism and reduced work productivity. A randomised and controlled study in employee-volunteers (with Perceived Stress Scale [PSS-14]>22) was performed to assess a mindfulness program based on brief integrated mindfulness practices (M-PBI) with the aim of reducing stress in the workplace. The PSS-14 of the employees before and after 8-weeks M-PBI program, as well as after a 20-week follow-up, was assessed (primary endpoint). The employees also carried the following questionnaires (secondary endpoints): Five Facet Mindfulness Questionnaire (FFMQ), Self-Compassion Scale (SCS), Experiences Questionnaire-Decentering (EQ-D), and Maslach Burnout Inventory-General Survey (MBI-GS). Heart Rate Variability (HRV) was measured during each session in a subgroup of employees (n = 10) of the interventional group randomly selected. A total of 40 employees (77.5% female median [SD] age of 36.6 [5.6] years) took part in this study: 21 and 19 in the intervention and control group, respectively. No differences in baseline characteristics were encountered between the groups. Results show a significant decrease in stress and increase in mindfulness over time in the intervention group (PSS-14 and FFMQ; p < 0.05 both). Additionally, an improvement in decentering (EQ-D), self-compassion (SCS) and burnout (MBI-GS) were also observed compared to the control group (p < 0.05 in all). HRV measurement also showed an improvement. In conclusion, a brief practices, 8-weeks M-BIP program is an effective tool to quickly reduce stress and improve well-being in a workplace.

Building Bridges for Innovation in Ageing: Synergies between Action Groups of the EIP on AHA.

The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).

DNA damage and p53 induction do not cause ZD1694-induced cell cycle arrest in human colon carcinoma cells.

Using four complementary approaches, ie., cell synchronization, bromodeoxyuridine labeling, and DNA and Western blot analyses, we investigated the underlying mechanism of cell cycle perturbation in response to ZD1694, a quinazoline-based antifolate thymidylate synthase inhibitor. With a single exposure at a concentration of 1 microM for 2 h, ZD1694 completely inhibits thymidylate synthase over 72 h and causes a sustained growth for at least 120 h, DNA damage, and p53 induction in human carcinoma cells. Although these cells displayed an S-phase block with the precise terminal arrest point depending on the timing of drug treatment in the cell cycle, their DNA-replicating machinery associated with polymerase alpha was preserved intact. When supplemented with exogenous dThd, these cells resumed an apparently normal S-phase progression for at least 4 h. Kinetic analyses based on synchronized cells indicate that S-phase arrest occurs first, preceding the induction of DNA double strand breaks and p53/p21. SW480 cells, in which p53mu failed to transduce p21, also exhibited the mode of S-phase arrest, essentially indistinguishable from that displayed by HCT-8 cells expressing the functional p53 (p53wt). That the DNA replication process is prerequisite for DNA double strand breaks was indicated by the following: (a) DNA damage occurred only when cells treated with ZD1694 progressed through S phase; and (b) the inhibition of DNA polymerase alpha by aphidicolin-blocked DNA damage. Based on the above, we conclude that S-phase arrest by ZD1694, with a subsequent damage of DNA double strands, is caused by the block of DNA synthesis in the middle of replication due to dTTP depletion and not by p53-mediated G1-G2 checkpoint mechanisms or p21-induced inactivation of the DNA-replicating machinery.

Time dependence of DNA lesions and growth inhibition by ICI D1694, a new quinazoline antifolate thymidylate synthase inhibitor.

DNA single-strand breaks and associated growth inhibition induced by the thymidylate synthase inhibitor N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazoline-6-ylmethyl)-N -methylamino]-2 - thenoyl)-L-glutamic acid (ICI D1694) were quantitated using the human ileocecal adenocarcinoma cell line, HCT-8. The effects of different concentrations and schedules of [6R,S]-5-formyltetrahydrofolate ([6RS]LV) and 2'-deoxy-thymidine (dThd) on drug growth inhibition and DNA damage were also evaluated. The drug concentrations for 50% inhibition of cell growth in culture following 2-h and 72-h exposures were 0.073 and 0.003 microM, respectively. After a 2-h drug exposure, the occurrence of DNA single-strand breaks (SSBs) was time dependent. It was detectable at 8 h and reached a maximum at about 24 h, 34 +/- 3 (SD) and 305 +/- 34 rad equivalents with 0.1 microM (50% inhibition concentration) and 1.0 microM (90% inhibition concentration) ICI D1694, respectively. A significant level of DNA SSBs (101 +/- 13 rad equivalents) was still detectable at 72 h after the 2-h treatment with 1 microM ICI D1694. No significant level of DNA SSBs was detected when cells were exposed simultaneously to ICI D1694 and 20 microM [6RS]LV. Complete rescue of drug-induced DNA SSBs could be achieved when cells were exposed to 10 microM dThd starting no later than 4 h after drug treatment. The growth inhibition of ICI D1694 was abrogated by [6RS]LV in a concentration-dependent manner. Complete protection was achieved when cells were exposed simultaneously to 1 microM ICI D1694 and 5 microMs [6RS]LV or to 3 microMs dThd immediately after drug treatment. The results demonstrate that: (a) the growth inhibition of ICI D1694 is a function of time and schedule; (b) the growth inhibition is accompanied by extensive DNA single-strand breaks and slow repair; (c) at 1 microM ICI D1694, 3 microMs dThd and 5 microMs [6RS]LV can completely rescue cells from drug effects when dThd is added up to 4 h following drug treatment or when [6RS]LV is given in combination with the drug; (d) interference of [6RS]LV with ICI D1694 action may be occurring at the level of drug uptake and at intracellular targets, while dThd interferes with the drug action at intracellular targets.

Regulation of copper uptake and transport in intestinal cell monolayers by acute and chronic copper exposure.

Adaptation to high and low copper intake in mammals depends on the cellular control of influx, efflux and storage mechanisms of cellular copper concentrations. In the present study, we used an intestinal cell line (Caco-2), grown in bicameral chambers to study the effect of equilibrium loading with copper. We analyzed (64)Cu uptake from the apical surface, intracellular metal (Cu, Zn, Fe) content, (64)Cu transport into the basal chamber, and total copper, zinc and iron in the basal chamber. We found that the (64)Cu uptake is saturable, shows a linear response phase up to 1.5 microM reaching a plateau at 4-6 microM extracellular Cu. Intracellular copper increased 21.6-fold, from 1.5 to 32.4 mM (at 0.2-20.2 microM extracellular copper respectively). The time course for (64)Cu uptake and transport was linear when the cells were incubated with different copper concentrations. Uptake increased 10-fold when intracellular copper concentration was raised. Fluxes were lowest at 1.5 mM and highest at 32.4 mM Cu intracellular copper (2.03 and 20. 98 pmole (64)Cu insert(-1) h(-1), respectively). The apical-to-basolateral copper transfer rate was lower at 32.4 mM as compared to 1.5 mM intracellular copper (0.55-1.95 pmole (64)Cu insert(-1) h(-1), respectively). The total copper in the basal chamber increased 4.2-fold (from 3.04 to 12.85 pmole Cu insert(-1) h(-1)) when the intracellular copper concentration was raised. If cells are preincubated in a low copper medium most of the newly incorporated copper (64%) is transferred to the basolateral compartment. In contrast, under preloading with high copper concentration, only 4% of the fresh copper is transferred to the basal chamber; however, the intracellular copper contribution to this chamber increases by 4.2-fold. Thus, the process results in an increase in both storage and intracellular-to-basolateral flux of copper. In summary, our results indicate that copper fluxes from apical-to-cell and apical-to-basolateral domains are affected by intracellular copper concentration suggesting that mechanisms of copper transport involved in cellular adaptation to low and high copper exposure are different.

Comparative assessment of glucose prediction models for patients with type 1 diabetes mellitus applying sensors for glucose and physical activity monitoring.

The present work presents the comparative assessment of four glucose prediction models for patients with type 1 diabetes mellitus (T1DM) using data from sensors monitoring blood glucose concentration. The four models are based on a feedforward neural network (FNN), a self-organizing map (SOM), a neuro-fuzzy network with wavelets as activation functions (WFNN), and a linear regression model (LRM), respectively. For the development and evaluation of the models, data from 10 patients with T1DM for a 6-day observation period have been used. The models' predictive performance is evaluated considering a 30-, 60- and 120-min prediction horizon, using both mathematical and clinical criteria. Furthermore, the addition of input data from sensors monitoring physical activity is considered and its effect on the models' predictive performance is investigated. The continuous glucose-error grid analysis indicates that the models' predictive performance benefits mainly in the hypoglycemic range when additional information related to physical activity is fed into the models. The obtained results demonstrate the superiority of SOM over FNN, WFNN, and LRM with SOM leading to better predictive performance in terms of both mathematical and clinical evaluation criteria.

Effectiveness of iron-fortified infant cereal in prevention of iron deficiency anemia.

BACKGROUND: Iron deficiency continues to be a common problem among infants throughout the world. Iron-fortified formula is effective in preventing iron deficiency but the benefit of iron-fortified cereal is controversial. METHODS: We compared iron-fortified rice cereal to unfortified rice cereal in infants who were exclusively breast-fed for more than 4 months and to iron-fortified formula in infants who were weaned to formula before 4 months of age. The design was double blind in respect to the presence or absence of fortification iron in the cereal or formula and included 515 infants who were followed on the protocol from 4 to 15 months of age. Rice cereal was fortified with 55 mg of electrolytic iron per 100 g of dry cereal and infant formula with 12 mg of ferrous sulfate per 100 g of dry powder, levels approximating those in use in the United States. Measures of iron status were obtained at 8, 12, and 15 months. Infants with hemoglobin levels of < 105 g/L were excluded from the study and treated. RESULTS: Consumption of cereal reached plateaus at means of about 30 g/d after 6 months of age in the formula-fed groups and 26 g/d after 8 months in the breast-fed groups; these amounts are higher than the 19-g/d mean intake by the 73% of infants who consume such cereal in the United States. Among infants weaned to formula before 4 months, the cumulative percentages of infants excluded for anemia by 15 months were 8%, 24%, and 4%, respectively, in the fortified cereal, unfortified cereal and formula, and fortified formula groups (P < .01 unfortified vs either fortified group; the difference between the two fortified groups was not significant). In infants breast-fed for more than 4 months, the corresponding values were 13% and 27%, respectively, in the fortified and unfortified cereal groups (P < .05). Mean hemoglobin level and other iron status measures were in accord with these findings. CONCLUSION: Iron-fortified infant rice cereal can contribute substantially to preventing iron deficiency anemia.

Down-regulation of c-myc gene expression with induction of high molecular weight DNA fragments by fluorodeoxyuridine.

5-Fluoro-2'-deoxyuridine (FdUrd), a potent inhibitor of thymidylate synthase, induces extensive bulk DNA damage at drug concentrations that produce significant in vitro growth inhibition of human ileocecal carcinoma (HCT-8) cells. Constant- and pulsed-field gel electrophoresis (CFGE and PFGE), to detect size distribution of DNA double-strand breaks and repair kinetics, in parallel with northern and western blot analyses, to quantitate c-myc gene and protein expression, were utilized to analyze drug effects. At 24-hr post in vitro drug treatment, when maximum bulk DNA damage was detected, FdUrd produced a broad range of high molecular weight DNA fragments, clustering between 0.1 and 5.7 megabases in size, and resulted in a decrease in the level of c-myc transcripts and protein with no significant effect on the level of v-myc and H-ras. These effects preceded the observed cellular growth inhibition. Addition of the reduced folate leucovorin potentiated the effects induced by FdUrd, indicating that thymidylate synthase inhibition is an important initial step in drug effect followed by DNA fragmentation and suppression of c-myc expression. Changes in the integrity of the genetic materials and regulatory genes occurred prior to the observed cell growth inhibition by FdUrd, suggesting that these molecular alterations by FdUrd may be associated with subsequent FdUrd-induced cell growth inhibition.

Telehygiene system for preventive chronopharmacology in space.

A remote computerized health care (telehygiene) system for space travel includes monitoring devices and pharmaceuticals aimed at the optimization of health and the environment. Early risk indicators are provided by dynamic characteristics of rhythms of several frequencies describing variation inside the physiologic range. These rhythm characteristics, assessed as one goes, can be updated and compacted as data accumulate by the use of chronobiologic software that resolves anticipated components of lower and lower frequency, thus providing summaries of data at intervals of differing length. At any time, harbingers of risk, including characteristics of circannual rhythms, can be retrieved in an instant. On their basis, early preventive action can be instituted for risk lowering and for delivery of timed treatment when needed. Preventive or curative health care in space and terrestrial spin-offs are the more effective the more of the chronome (time-structure) is resolved.

Effect of amiodarone on ventricular fibrillation and defibrillation thresholds in the canine heart under normal and ischemic conditions.

The main goal of this project was to study the effect of amiodarone upon ventricular fibrillation and defibrillation thresholds (VFT and VDT) in the canine heart under normal and ischemic conditions. Both parameters were assessed in 11 dogs, each experiment consisting of three consecutive phases: (a) control, which resulted in VFT = 27.9 (S.D. = 15.5) and VDT = 43.9 (S.D. = 4.5); (b) drug, with VFT = 63.5 (S.D. = 32.8) and VDT = 57.8 (S.D. = 11.3), and (c) coronary occlusion, with VFT = 44.7 (S.D. = 21.6) and VDT = 57.1 (S.D. = 11.0). These values are overall means scaled to ventricular weight (microA/g for VFT and mA/g for VDT). Both VFT and VDT in (b) and (c) were, on the average, greater than in (a) and these differences were statistically significant (P less than 0.01, paired t-test). The animals were kept normothermic (37.3 degrees C, S.D. = 0.6) within normal values for the acid-base state. We concluded that amiodarone increased the VFT significantly. Similarly, it increased VDT. However, although the latter change was statistically significant, we believe it would not be important from a physiological or clinical point of view.

Imipramine prevents gastric lesions induced by centrally administered thyrotropin-releasing hormone (TRH) in rats.

Increasing evidence indicates that thyrotropin-releasing hormone (TRH), and endogenous brain-gut peptide may play a role in experimental ulcerogenesis. Potential interactions between TRH and imipramine (a typical tricyclic antidepressant (TCA] on the development of TRH-induced gastric lesions have not been investigated. Imipramine (0.05, 0.5 and 5 mg/kg, i.p.) dose-dependently inhibited gastric lesion formation induced by intracisternal (i.c.) administration of TRH (1 micrograms). In addition, imipramine (5 mg/kg, i.p.) significantly decreased gastric acid secretion in response to i.c. TRH (1 microgram) in rats with pyloric ligation. These findings suggest the TCAs may be effective drug agents against centrally initiated gastric ulcerations. The mechanism of this response probably involves blockade of cholinergic (muscarinic) and H2 histamine receptors.

Evidence for a role of brain thyrotropin-releasing hormone (TRH) on stress gastric lesion formation in rats.

Specific polyclonal antibodies raised against synthetic thyrotropin-releasing hormone (TRH) infused intracerebroventricularly (ICV) significantly decreased gastric lesions induced by cold restraint stress. The antiulcer effect of immunologic blockade of brain TRH was specific. Normal rabbit serum or antibodies raised against somatostatin, alpha-MSH, Leu-enkephalin, gonadotropin-releasing hormone and atrial natriuretic factor were ineffective. These findings suggest that brain TRH may play an important role in experimental stress ulcer formation.