Four-hour infusions of synthetic atrial natriuretic peptide in normal volunteers.

Two doses of synthetic atrial natriuretic peptide (0.5 and 5.0 micrograms/min) and its vehicle were infused intravenously for 4 hours in eight salt-loaded normal volunteers, and the effect on blood pressure, heart rate, renal hemodynamics, solute excretion, and secretion of vasoactive hormones was studied. The 0.5 micrograms/min infusion did not alter blood pressure or heart rate, whereas the 5.0 micrograms/min infusion significantly reduced the mean pressure by 20/9 mm Hg after 2.5 to 3 hours and increased the heart rate slightly. Inulin clearance was not significantly changed, but the mean p-aminohippurate clearance fell by 13 and 32% with the lower and higher doses, respectively. Urinary excretion of sodium and chloride increased slightly with the lower dose. With the higher dose, a marked increase in urinary excretion of sodium, chloride, and calcium was observed, reaching a peak during the second hour of the infusion. Potassium and phosphate excretion did not change significantly. A brisk increase in urine flow rate and fractional water excretion was seen only during the first hour of the high-dose infusion. Signs and symptoms of hypotension were observed in two subjects. No change in plasma renin activity, angiotensin II, or aldosterone was observed during either infusion, but a marked increase occurred after discontinuation of the high-dose infusion. In conclusion, the 5 micrograms/min infusion induced a transient diuretic effect, delayed maximal natriuretic activity, and a late fall in blood pressure, with no change in inulin clearance but a dose-related decrease in p-aminohippurate clearance. Despite large amounts of sodium excreted and blood pressure reduction, no counterregulatory changes were observed in the renin-angiotensin-aldosterone system or plasma vasopressin levels during the infusion.

Sodium and potassium balance depends on αENaC expression in connecting tubule.

Mutations in α, β, or γ subunits of the epithelial sodium channel (ENaC) can downregulate ENaC activity and cause a severe salt-losing syndrome with hyperkalemia and metabolic acidosis, designated pseudohypoaldosteronism type 1 in humans. In contrast, mice with selective inactivation of αENaC in the collecting duct (CD) maintain sodium and potassium balance, suggesting that the late distal convoluted tubule (DCT2) and/or the connecting tubule (CNT) participates in sodium homeostasis. To investigate the relative importance of ENaC-mediated sodium absorption in the CNT, we used Cre-lox technology to generate mice lacking αENaC in the aquaporin 2-expressing CNT and CD. Western blot analysis of microdissected cortical CD (CCD) and CNT revealed absence of αENaC in the CCD and weak αENaC expression in the CNT. These mice exhibited a significantly higher urinary sodium excretion, a lower urine osmolality, and an increased urine volume compared with control mice. Furthermore, serum sodium was lower and potassium levels were higher in the genetically modified mice. With dietary sodium restriction, these mice experienced significant weight loss, increased urinary sodium excretion, and hyperkalemia. Plasma aldosterone levels were significantly elevated under both standard and sodium-restricted diets. In summary, αENaC expression within the CNT/CD is crucial for sodium and potassium homeostasis and causes signs and symptoms of pseudohypoaldosteronism type 1 if missing.

Development of a hepatocyte hollow fiber bioreactor for the study of contrast agents by magnetic resonance imaging

Thanks to the continuous progress made in recent years, medical imaging has become an important tool in the diagnosis of various pathologies. In particular, magnetic resonance imaging (MRI) permits to obtain images with a remarkably high resolution without the use of ionizing radiation and is consequently widely applied for a broad range of conditions in all parts of the body. Contrast agents are used in MRI to improve tissue discrimination. Different categories of contrast agents are clinically available, the most widely used being gadolinium chelates. One can distinguish between extracellular gadolinium chelates such as Gd-DTPA, and hepatobiliary gadolinium chelates such as Gd-BOPTA. The latter are able to enter hepatocytes from where they are partially excreted into the bile to an extent dependent on the contrast agent and animal species. Due to this property, hepatobiliary contrast agents are particularly interesting for the MRI of the liver. Actually, a change in signal intensity can result from a change in transport functions signaling the presence of impaired hepatocytes, e.g. in the case of focal (like cancer) or diffuse (like cirrhosis) liver diseases. Although the excretion mechanism into the bile is well known, the uptake mechanisms of hepatobiliary contrast agents into hepatocytes are still not completely understood and several hypotheses have been proposed. As a good knowledge of these transport mechanisms is required to allow an efficient diagnosis by MRI of the functional state of the liver, more fundamental research is needed and an efficient MRI compatible in vitro model would be an asset. So far, most data concerning these transport mechanisms have been obtained by MRI with in vivo models or by a method of detection other than MRI with cellular or sub-cellular models. Actually, no in vitro model is currently available for the study and quantification of contrast agents by MRI notably because high cellular densities are needed to allow detection, and no metallic devices can be used inside the magnet room, which is incompatible with most tissue or cell cultures that require controlled temperature and oxygenation. The aim of this thesis is thus to develop an MRI compatible in vitro cellular model to study the transport of hepatobiliary contrast agents, in particular Gd-BOPTA, into hepatocytes directly by MRI. A better understanding of this transport and especially of its modification in case of hepatic disorder could permit in a second step to extrapolate this knowledge to humans and to use the kinetics of hepatobiliary contrast agents as a tool for the diagnosis of hepatic diseases.

Comparative efficacy of chelators to remove renal cadmium burden in isolated perfused rat kidneys

Trois agents chélateurs (l?acide diéthylène triamine penta-acétique, DTPA; l?acide méso-2,3- dimercaptosucchique, DMSA; l?acide 2,3-dimercapto- 1 -propanesulfonique, DMPS) ont été comparés quant à leur efficacité à mobiliser du cadmium (Cd) accumulé dans le tissu rénal. Des reins prélevés chez des rats exposés durant 3 j au Cd (acétate de Cd , 0.75 mg/kg.j, i.p) ont été isolés et perfusés in vitro, à l?aide d?un système de reperfusion utilisant une solution de Krebs-Henseleit, pH 7.4, contenant 8 acides aminés et 6% d?albumine. Les concentrations de Cd dans le perfusat et l?urine ont été mesurées par spectrométrie d?absorption atomique. Six périodes de clearance, après une période d?équilibration de 20 min, ont ?été obtenues. Le DMSA et le DMPS ont mobilisé le Cd à partir du tissu rénal, comme l?ont montré les augmentations dose-dépendantes des concentrations de Cd dans l?urine et le perfusat. L?accumulation de Cd était nettement plus élevée dans le perfusat que dans l?urine, indiquant que l?effet des chélateurs se marquait surtout au niveau tubulaire basolatéral. Le DTPA n?induisait qu?une faible mobilisation de Cd dans l?urine et le perfusat, et son efficacité était clairement inférieure à celle des autres chélateurs. Comme prévu, la quantité de Cd présente dans le tissu rénal après perfùsion par le DMSA ou le DMPS diminuait en fonction de l?efficacité des chélateurs, jusqu?à des valeurs inférieures de 46% au taux rénal de Cd avant perfusion. Le DMPS apparaissait induire une excretion urinaire de Cd plus importante que celle induite par le DMSA, une caractéristique qui pourrait être liée à une sécrétion tubulaire du chélateur, qui a été décrite antérieurement. Un intervalle de temps prolongé (1 -2 semaines) entre le moment de l?administration du Cd et la perfusion du rein avec le DMPS induisait une augmentation de l?excrétion urinaire de Cd. Tous les chélateurs se sont montrés néphrotoxiques à concentrations élevées.

Relación entre el nivel de grasa e ingestión y la excreción urinaria de nitrógeno y energía, en gazapos en crecimiento-cebo

Se determinó la excreción urinaria de nitrógeno (NU, %) y de energía (EU, kcal/100g), en la última semana de vida, de 36 conejos alimentados, desde el destete (a los 28 d) hasta el sacrificio a los dos meses de edad, con tres piensos conteniendo 0, 3 y 6 % de grasa añadida (G0, G3 y G6); y administrados a dos niveles de ingestión: ad libitum (IL) y restringido (IR) al 70 % de IL. El NU y la EU estuvieron influidos positivamente tanto por el nivel de ingestión (P<0,001) como por el % de grasa ingerida (P<0,05). En estos resultados puede estar involucrado el metabolismo tan elevado de las lipoproteínas transportadoras de lípidos, implicadas en el metabolismo de las grasas, ya sean de origen alimentario o de la lipogénesis de novo. La relación entre la EU y el NU aporta valores muy superiores a los que podría corresponder a las materias orgánicas nitrogenadas, por lo que se podría pensar, como posible causa, en la intervención de materia orgánica no nitrogenada. Asimismo, la cuantificación de la EM del pienso se ve afectada por el incremento del valor calórico de la orina, con el nivel de ingestión y/o el 6 % de grasa añadida. Con ello se evidencia la desigualdad entre ED y EM de la grasa en las raciones que las incluya. Asimismo, el hecho de que la movilización grasa —bien sea de origen alimentario o de la lipogénesis— altere la excreción nitrogenada y/o energética a través de la orina, pone de manifiesto la importancia de su consideración, especialmente cuando dicha pérdida puede afectar a los rendimientos de algunas producciones animales.

A prospective observational study comparing a non-operator dependent automatic PWV analyser to pulse pressure, in assessing arterial stiffness in hemodialysis.

BACKGROUND: Chronic kidney disease (CKD) accelerates vascular stiffening related to age. Arterial stiffness may be evaluated measuring the carotid-femoral pulse wave velocity (PWV) or more simply, as recommended by KDOQI, monitoring pulse pressure (PP). Both correlate to survival and incidence of cardiovascular disease. PWV can also be estimated on the brachial artery using a Mobil-O-Graph; a non-operator dependent automatic device. The aim was to analyse whether, in a dialysis population, PWV obtained by Mobil-O-Graph (MogPWV) is more sensitive for vascular aging than PP. METHODS: A cohort of 143 patients from 4 dialysis units has been followed measuring MogPWV and PP every 3 to 6 months and compared to a control group with the same risk factors but an eGFR > 30 ml/min. RESULTS: MogPWV contrarily to PP did discriminate the dialysis population from the control group. The mean difference translated in age between the two populations was 8.4 years. The increase in MogPWV, as a function of age, was more rapid in the dialysis group. 13.3% of the dialysis patients but only 3.0% of the control group were outliers for MogPWV. The mortality rate (16 out of 143) was similar in outliers and inliers (7.4 and 8.0%/year). Stratifying patients according to MogPWV, a significant difference in survival was seen. A high parathormone (PTH) and to be dialysed for a hypertensive nephropathy were associated to a higher baseline MogPWV. CONCLUSIONS: Assessing PWV on the brachial artery using a Mobil-O-Graph is a valid and simple alternative, which, in the dialysis population, is more sensitive for vascular aging than PP. As demonstrated in previous studies PWV correlates to mortality. Among specific CKD risk factors only PTH is associated with a higher baseline PWV. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02327962.

Applying precision feeding techniques in growing-finishing pig operations

The high cost of feed ingredients, the use of non-renewable sources of phosphate and the dramatic increase in the environmental load resulting from the excessive land application of manure are major challenges for the livestock industry. Precision feeding is proposed as an essential approach to improve the utilization of dietary nitrogen, phosphorus and other nutrients and thus reduce feeding costs and nutrient excretion. Precision feeding requires accurate knowledge of the nutritional value of feedstuffs and animal nutrient requirements, the formulation of diets in accordance with environmental constraints, and the gradual adjustment of the dietary nutrient supply to match the requirements of the animals. After the nutritional potential of feed ingredients has been precisely determined and has been improved by the addition of enzymes (e.g. phytases) or feed treatments, the addition of environmental objectives to the traditional feed formulation algorithms can promote the sustainability of the swine industry by reducing nutrient excretion in swine operations with small increases in feeding costs. Increasing the number of feeding phases can also contribute to significant reductions in nutrient excretion and feeding costs. However, the use of precision feeding techniques in which pigs are fed individually with daily tailored diets can further improve the efficiency with which pigs utilize dietary nutrients. Precision feeding involves the use of feeding techniques that allow the provision of the right amount of feed with the right composition at the right time to each pig in the herd. Using this approach, it has been estimated that feeding costs can be reduced by more than 4.6%, and nitrogen and phosphorus excretion can both be reduced by more than 38%. Moreover, the integration of precision feeding techniques into large-group production systems can provide real-time off-farm monitoring of feed and animals for optimal slaughter and production strategies, thus improving the environmental sustainability of pork production, animal well-being and meat-product quality.

Biological impact assessment of nanomaterial used in nanomedicine. Introduction to the NanoTEST project.

Therapeutic nanoparticles (NPs) are used in nanomedicine as drug carriers or imaging agents, providing increased selectivity/specificity for diseased tissues. The first NPs in nanomedicine were developed for increasing the efficacy of known drugs displaying dose-limiting toxicity and poor bioavailability and for enhancing disease detection. Nanotechnologies have gained much interest owing to their huge potential for applications in industry and medicine. It is necessary to ensure and control the biocompatibility of the components of therapeutic NPs to guarantee that intrinsic toxicity does not overtake the benefits. In addition to monitoring their toxicity in vitro, in vivo and in silico, it is also necessary to understand their distribution in the human body, their biodegradation and excretion routes and dispersion in the environment. Therefore, a deep understanding of their interactions with living tissues and of their possible effects in the human (and animal) body is required for the safe use of nanoparticulate formulations. Obtaining this information was the main aim of the NanoTEST project, and the goals of the reports collected together in this special issue are to summarise the observations and results obtained by the participating research teams and to provide methodological tools for evaluating the biological impact of NPs.

Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

Korkeavaaleuksisen PGW-massan valmistaminen

Työssä haettiin optimaalista valkaisukemikaalien annostelusuhdetta mahdollisimman vaalean massan valmistamiseksi. Tarkoituksena oli myös selvittää käytettävän tehdasprosessin pullonkauloja ja esittää vaihtoehtoja prosessin kehittämiseksi. Kirjallisuusosassa tutustuttiin mekaanisen massan peroksidivalkaisuun ja erilaisiin prosessimalleihin sen suorittamiseksi. Kirjallisuudesta saatuja lähtötietoja sovellettiin sitten ensin laboratorio- ja laajemmin tehdaskokein käytäntöön. Laboratoriokokeissa haettiin optimaalista lipeäannosta vakioperoksidiannoksella. Lisäksi selvitettiin lämpötilan ja viipymäajan vaikutusta valkaisutulokseen. Tuloksista oli todettavissa, että sekä lämpötilan että lipeäannoksen kasvattaminen kiihdyttää valkaisureaktiota. Korkeammassa lämpötilassa tarvittava lipeäannos on pienempi. Lyhyellä viipymäajalla ja matalammalla lämpötilalla saavutetaan hyviä tuloksia vain suurella lipeäannoksella. Suurempaa silikaattiannosta käytettäessä valkaisun jälkeen mitattu loppupH oli korkeampi ja jäännösperoksidin määrä hieman suurempi kuin referenssipisteessä. Vaaleudessa ei merkittävää muutosta näkynyt. Yleisesti laboratoriokokeiden tulokset vastasivat kirjallisuudessa esitettyjä tuloksia. Tehdaskokeet suoritettiin kahdella peroksidiannoksella. Kummallekin peroksidiannokselle haettiin optimaalinen lipeäannos. Lisäksi seurattiin silikaattiannoksen vaikutusta syntyvään vaaleuteen. Varsinaisten kokeiden lisäksi suoritettiin lyhyt maksimivaaleuskoe suurella peroksidiannoksella käyttäen kahta eri lipeäannosta. Suurin mitattu vaaleus oli 79,3 % ISO. Peroksidiannoksella 2,5 % saavutettiin noin 14 ISO-yksikön vaaleudennousu, ja annoksella 3 % vaaleudennousu oli noin 16 yksikköä. Tehdaskokeiden aikana kokeiltiin myös kemikaalien laimennusveden määrän vaikutusta vaaleuteen. Veden määrän vähetessä valkaisusakeus nousi ja vaaleus parani. Hiomon nykyprosessille laadittiin aine- ja energiatase. Taseet tehtiin myös prosessille, jossa nykyvalkaisimoon on lisätty valkaistun massan pesu ja jäännöskemikaalien kierrätys. Taseiden tarkoituksena oli selvittää virtaavien jakeiden määriä ja prosessin energiatasapainoa eri tilanteissa. Massan puhtauden paranemista pesun aikana tarkasteltiin laskennallisesti. Tämän työn aikana kävi selväksi, että oikeilla valkaisukemikaalisuhteilla pystytään valmistamaan vaaleaa massaa. Viipymäaikaa lisäämällä valkaisuun saisi lisää tehoa, mutta vain tunnin viipymäajalla päästään jo hyviin tuloksiin. Vaaleusheittoja aiheuttavat valkaistavan massan lähtövaaleuden, sakeuden ja lämpötilan muutokset. Lisäksi viipymäajan muutokset aiheuttavat huojuntaa saavutettavaan loppuvaaleuteen.

Electronic Commerce - Advantages and Requirements through Supply Chain

Työ käsittelee Metso Paper Servicen varaosa- ja kulutusosatuotelinjojen mahdollisuuksia sähköiseen liiketoimintaan ulkoisten asiakkaiden kanssa sekä sähköisten transaktioiden vaikutuksia, etuja ja edellytyksiä. Työssä selvitetään Metson ja sen kymmenen kotimaisen asiakastehtaan myynti- ja ostoprosessin toiminta. Prosessimallin avulla arvioidaan valmiuksia sähköisiin transaktioihin nykyisessä myynti- ja ostotoiminnassa. Tarkastelu painottuu toimintoihin tarjontaketjun eri vaiheissa. Teknisiä näkökohtia käsitellään kokonaiskuvan luomiseksi. Lisäksi työssä arvioidaan muutoksia, joita sähköinen liiketoiminta aiheuttaisi. Haastatteluin tehdyssä tutkimuksessa kartoitetaan näkemyksiä sähköiseen liiketoimintaan erilaisilla organisaation tasoilla. Kokonaisnäkemys syntyy erilaisista näkökulmista sähköiseen kauppaan. Sähköiseen liiketoimintaan suhtaudutaan myönteisesti. Kokemuksia on kuitenkin vielä vähän. Vaikka hankkeita sähköisen liiketoiminnan lisäämiseksi on vireillä, yhtä tärkeää on parantaa valmiuksia tehostamalla paitsi informaatiovirtaa, myös materiaalivirtaa.

Muutos- ja oppimisprosessin johtaminen teollisuusyrityksessä

Kilpailukeinojen muuttuessa teollisuusyritysten muutostarve nopeutuu. Tämä aiheuttaa yritysten henkilökunnalle uusia haasteita ja lisää paineita elinikäiseen oppimiseen. Samalla se aiheuttaa koko yrityksen organisaatiolle yhteisen oppimisen tarpeen eli muuttumisen oppivaksi organisaatioksi. työssä on tutkittu oppivan organisaation käsitettä, valmiuksia muutosjohtamiseen sekä tarvittavaa asennetta muutosten tehokkaaseen läpivientiin. Muutoksen johtamiseen on esitetty muutosmallia, jonka sovellettavuutta on arvioitu case-yrityksen avulla. Muutosasenteen lisäksi on kiinnitetty huomiota mittaamiseen ja muutosten jatkumiseen päättymättöminä prosesseina. Työn tulokseksi saatiin mm. seuraavia toimenpide-ehdotuksia: Koulutusta tulisi lisätä ylimmälle johdole ja mielipidevaikuttajille. Organisaatiota pitäisi muuttaa tiedonkulkua suosivaksi ja saattaa tietojärjestelmät joustaviksi ja muutoksia tukeviksi järjestelmmiksi.

Absorption and pharmacokinetics of green tea catechins in beagles

The present study evaluates for the first time in dogs, the kinetics of green tea catechins and their metabolic forms in plasma and urine. Ten beagles were administered 173 mg (12·35 mg/kg body weight) of catechins as a green tea extract, in capsules. Blood samples were collected during 24 h after intake and urine samples were collected during the following periods of time: 0-2, 2-6, 6-8 and 8-24 h. Two catechins with a galloyl moiety and three conjugated metabolites were detected in plasma. Most of the detected forms in plasma reached their maximum plasma concentration (Cmax) at around 1 h. Median Cmax for (2)-epigallocatechin-3-gallate (EGCG), (2)-epicatechin-3-gallate (ECG), (2)-epigallocatechin glucuronide (EGCglucuronide), (2)-epicatechin glucuronide (EC-glucuronide), (2)-epicatechin sulphate (EC sulphate) were 0·3 (range 0·1-1·9), 0·1 (range 0-0·4), 0·8 (range 0·2-3·9), 0·2 (range 0·1 1·7) and 1 (range 0·3-3·4) mmol/l, respectively. The areas under the plasma concentration v. time curves (AUC0!24) were 427 (range 102-1185) mmol/l £ min for EGC-glucuronide, 112 (range 53-919) mmol/l £ min for EC-sulphate, 71 (range 26-306) mmol/l £ min for EGCG, 40 (range 12-258) mmol/l £ min for EC-glucuronide and 14 (range 0·1-124) mmol/l £ min for ECG. The values of mean residence time (MRT0!24) were 5 (range 2-16), 2 (range 1-11), 10 (range 2-13), 3 (range 2-16) and 2·4 (range 1-18) h for EGCG, ECG, EGC-glucuronide, EC-glucuronide and EC sulphate, respectively. In urine, catechins were present as conjugated forms, suggesting bile excretion of EGCG and ECG. Green tea catechins are absorbed following an oral administration and EGC-glucuronide is the metabolic form that remains in the organism for a longer period of time, suggesting that this compound could suffer an enterohepatic cycle.

Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide.

Sucroferric oxyhydroxide (VELPHORO(®)) is a polynuclear iron-based phosphate binder recently approved for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). As a number of the available phosphate binders do not provide the optimal combination of good efficacy, adequate tolerability and low pill burden, sucroferric oxyhydroxide constitutes a promising alternative. Among the attributes of an ideal phosphate binder is minimal absorption and, hence, low risk of systemic toxicity. Accordingly, the iron-releasing properties and absorption, distribution, metabolism and excretion (ADME) profile of sucroferric oxyhydroxide, as well as the possibility of iron accumulation and toxicity, were investigated in a series of preclinical studies. The effect of sucroferric oxyhydroxide on the progression of vascular calcification was also investigated. Sucroferric oxyhydroxide exhibited a high phosphate-binding capacity and low iron-releasing properties across the physiological pH range found in the gastrointestinal tract. In the ADME studies, uptake of (59)Fe-radiolabelled sucroferric oxyhydroxide was low in rats and dogs (<1% from a 50 mg Fe/kg bodyweight dose), with the majority of absorbed iron located in red blood cells. Long-term (up to 2 years) administration of sucroferric oxyhydroxide in rats and dogs was associated with modest increases in tissue iron levels and no iron toxicity. Moreoever, in uraemic rats, sucroferric oxyhydroxide was associated with reduced progression of vascular calcification compared with calcium carbonate. In conclusion, sucroferric oxyhydroxide offers a new option for the treatment of hyperphosphataemia, with a high phosphate-binding capacity, minimal iron release, and low potential for iron accumulation and toxicity.

Absorption and pharmacokinetics of green tea catechins in beagles

The present study evaluates for the first time in dogs, the kinetics of green tea catechins and their metabolic forms in plasma and urine. Ten beagles were administered 173 mg (12·35 mg/kg body weight) of catechins as a green tea extract, in capsules. Blood samples were collected during 24 h after intake and urine samples were collected during the following periods of time: 0-2, 2-6, 6-8 and 8-24 h. Two catechins with a galloyl moiety and three conjugated metabolites were detected in plasma. Most of the detected forms in plasma reached their maximum plasma concentration (Cmax) at around 1 h. Median Cmax for (2)-epigallocatechin-3-gallate (EGCG), (2)-epicatechin-3-gallate (ECG), (2)-epigallocatechin glucuronide (EGCglucuronide), (2)-epicatechin glucuronide (EC-glucuronide), (2)-epicatechin sulphate (EC sulphate) were 0·3 (range 0·1-1·9), 0·1 (range 0-0·4), 0·8 (range 0·2-3·9), 0·2 (range 0·1 1·7) and 1 (range 0·3-3·4) mmol/l, respectively. The areas under the plasma concentration v. time curves (AUC0!24) were 427 (range 102-1185) mmol/l £ min for EGC-glucuronide, 112 (range 53-919) mmol/l £ min for EC-sulphate, 71 (range 26-306) mmol/l £ min for EGCG, 40 (range 12-258) mmol/l £ min for EC-glucuronide and 14 (range 0·1-124) mmol/l £ min for ECG. The values of mean residence time (MRT0!24) were 5 (range 2-16), 2 (range 1-11), 10 (range 2-13), 3 (range 2-16) and 2·4 (range 1-18) h for EGCG, ECG, EGC-glucuronide, EC-glucuronide and EC sulphate, respectively. In urine, catechins were present as conjugated forms, suggesting bile excretion of EGCG and ECG. Green tea catechins are absorbed following an oral administration and EGC-glucuronide is the metabolic form that remains in the organism for a longer period of time, suggesting that this compound could suffer an enterohepatic cycle.