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51.
Barley (Hordeum vulgare L.) malt contains endoproteinases belonging to all four of the commonly occurring classes, including serine proteinases. It also contains low molecular weight proteins that inhibit the activities of many of these endoproteinases, but it had never been shown that any barley or malt serine proteinases could be inhibited by any of these endogenous proteins. It is now reported that some proteins that were concentrated using an "affinity" method inhibited the activity of a malt serine endoproteinase. Two-dimensional electrophoretic and in vitro analyses showed that the inhibited enzyme was serine endoproteinase 1 (SEP-1) and that the inhibition could be quantified using a semipurified preparation of this enzyme. Amino acid sequencing and MALDI-TOF MS were used to identify the components of the partially purified inhibiting fractions. Only the "trypsin/alpha-amylase inhibitors" or chloroform/methanol (CM) proteins, most of which had truncated N and C termini, and one fragment of beta-amylase were present in the inhibitory fractions. When a CM protein fraction was prepared from barley according to traditional methods, some of its component proteins inhibited the activity of SEP-1 and some did not. This is the first report of the purification and identification of barley malt proteins that can inhibit an endogenous serine proteinase. It shows that some of the CM proteins probably play a role in controlling the activity of barley proteinases during germination, as well as possibly protecting the seed and young plant from microbes or pests. 相似文献
52.
Irene Sartini Beata ebkowska‐Wieruszewska Andrzej Lisowski Amnart Poapolathep Barbara Cuniberti Mario Giorgi 《Journal of veterinary pharmacology and therapeutics》2021,44(1):28-35
Acetaminophen (paracetamol) is used in dogs to manage fever and mild pain. The aim of this study was to assess the pharmacokinetics of acetaminophen in both fed and fasted Labrador Retrievers after a single intravenous and oral administration (20 mg/kg). Six healthy dogs underwent three treatments in a randomized block study (a, n = 2; b, n = 2; c, n = 2). In phase one, group a received acetaminophen intravenously, group b and c orally after being fasted and fed, respectively. In phase two and three, groups were swapped, and the experiment was repeated. At the end of the trial, each dog received the same treatment. Acetaminophen plasma concentrations were detected using a validated HPLC‐UV method. The pharmacokinetic analysis was performed using a noncompartmental model. Clearance, volume at steady state and half‐life of acetaminophen in Labrador Retrievers were 0.42 L/kg hr, 0.87 L/kg and 1.35 hr, respectively. No significant statistical differences were found between fasted and fed dogs regarding maximum plasma concentration, time at maximum concentration and bioavailability as measured by the AUC. Feeding does not significantly affect the acetaminophen oral pharmacokinetics. 相似文献
53.
Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk 下载免费PDF全文
Tae Won Kim Andrejs Sitovs Amnart Poapolathep Helen Owen Andrzej Lisowski Zulkyya Abilova Mario Giorgi 《Journal of veterinary pharmacology and therapeutics》2018,41(5):699-705
Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue. 相似文献
54.
Mengozzi G Intorre L Bertini S Giorgi M Secchiari PL Soldani G 《Research in veterinary science》2002,73(3):291-295
Eight healthy Holstein-Friesian calves and 8 Massese lambs of either sex (10-15-days old) were used to evaluate the pharmacokinetics of thiamphenicol after intravenous (i.v.) and oral (p.o.) administration (30 mg/kg). Plasma concentrations of thiamphenicol were determined by high-performance liquid chromatography on blood samples collected over 24h following treatment. Pharmacokinetic variables of the drug were calculated for both species and after both administration routes. After intravenous administration of thiamphenicol, a rapid distribution phase was followed by a slower elimination phase and, when thiamphenicol was administered p.o., the bioavailability was about 60% in both species. The higher volume of distribution and the longer biological elimination half-lives in pre-ruminant compared with adult animals indicate that thiamphenicol distributes widely into the extravascular compartment of pre-ruminants. Interspecies differences were observed in the kinetic behaviour of thiamphenicol with respect to peak plasma concentration (C(max)), time of peak plasma concentration (T(max)), elimination half-life (T(1/2)) and total clearance (Cl(B)). In conclusion intravenous or oral administration of 30 mg/kg of thiamphenicol provides plasma concentrations higher than minimum effective concentrations inhibiting bacterial growth (MICs) against most pathogens in pre-ruminant lambs and calves. 相似文献
55.
Giorgi C Ito K Lin HK Santangelo C Wieckowski MR Lebiedzinska M Bononi A Bonora M Duszynski J Bernardi R Rizzuto R Tacchetti C Pinton P Pandolfi PP 《Science (New York, N.Y.)》2010,330(6008):1247-1251
The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such a diverse proapoptotic role is currently unknown. We show that extranuclear Pml was specifically enriched at the endoplasmic reticulum (ER) and at the mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca(2+)) transport and in induction of apoptosis. We found Pml in complexes of large molecular size with the inositol 1,4,5-trisphosphate receptor (IP(3)R), protein kinase Akt, and protein phosphatase 2a (PP2a). Pml was essential for Akt- and PP2a-dependent modulation of IP(3)R phosphorylation and in turn for IP(3)R-mediated Ca(2+) release from ER. Our findings provide a mechanistic explanation for the pleiotropic role of Pml in apoptosis and identify a pharmacological target for the modulation of Ca(2+) signals. 相似文献
56.
Pharmacokinetic profiles of the active metamizole metabolites after four different routes of administration in healthy dogs 下载免费PDF全文
M. Giorgi B. Łebkowska‐Wieruszewska A. Lisowski H. Owen A. Poapolathep T. W. Kim V. De Vito 《Journal of veterinary pharmacology and therapeutics》2018,41(3):428-436
Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4‐methylaminoantipyrine (MAA) and relatively active secondary metabolite 4‐aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single‐dose, four‐treatment, four‐phase, unpaired, crossover study design. Blood was collected at predetermined times within 24 hr, and plasma was analyzed by a validated HPLC‐UV method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC) min to 24 hr in all dogs. The highest concentrations of MAA were found in the i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar for i.v., i.m., and RC, and the concentrations were approximately double those in the PO groups. The AUCEV/IV ratio for MAA was 0.75 ± 0.11, 0.59 ± 0.08, and 0.32 ± 0.05, for i.m., p.o., and RC, respectively. The AUCEV/IV ratio for AA was 1.21 ± 0.33, 2.17 ± 0.62, and 1.08 ± 0.19, for i.m., p.o., and RC, respectively. Although further studies are needed, rectal administration seems to be the least suitable route of administration for MT in the dog. 相似文献
57.
M. Giorgi S. Aupanun H.‐K. Lee A. Poapolathep R. Rychshanova C. Vullo V. Faillace F. Laus 《Journal of veterinary pharmacology and therapeutics》2017,40(2):165-171
Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4‐methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among the other secondary metabolites, 4‐aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 × 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC‐UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC0‐last of MAA were statistically different between the i.v. and i.m. groups. The AUCIM/AUCIV ratio of MAA was 1.06. In contrast, AUC0‐last of AA was statistically different between the groups (P < 0.05) with an AUCIM/AUCIV ratio of 0.54. This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug. 相似文献
58.
59.
C A Santa Rosa C R Sulzer W Giorgi A S da Silva R M Yanaguita A O Lobao 《American journal of veterinary research》1975,36(9):1363-1365
A new leptospiral serotype in the serogroup Pyrogenes is described. The strain was isolated from one gray "four-eyed" opossum (Philander opossum). It is proposed that the serotype be designated guaratuba, strain An-7705. The isolations of serotypes ballum from the South American field mouse (Akodon arviculoides), szwajizak and icterohaemorrhagiae from the North American opossum (Didelphis marsupialis), and grippotyphosa from many other wild animal species as well as domesticated animals are also described. 相似文献
60.
Natsuda Raweewan Weerapong Laovechprasit Mario Giorgi Thanaphan Chomcheun Narumol Klangkaew Kanjana Imsilp Amnart Poapolathep Saranya Poapolathep 《Journal of veterinary pharmacology and therapeutics》2020,43(2):135-140
To the best of our knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for Hawksbill turtles. Therefore, the present study aimed to assess the pharmacokinetic features of tolfenamic acid (TA) in Hawksbill turtles, Eretmochelys imbricata, after single intravenous (i.v.) and intramuscular (i.m.) administration at dosage 4 mg/kg body weight (b.w.). The study (parallel design) used 10 Hawksbill turtles randomly divided into equal groups. Blood samples were collected at assigned times up to 144 hr. The concentrations of TA in plasma were quantified by a validated liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). The concentration of TA in the experimental turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The Cmax values of TA were 89.33 ± 6.99 µg/ml following i.m. administration. The elimination half-life values were 38.92 ± 6.31 hr and 41.09 ± 9.32 hr after i.v. and i.m. administration, respectively. The absolute i.m. bioavailability was 94.46%, and the average binding percentage of TA to plasma protein was 31.39%. TA demonstrated a long half-life and high bioavailability following i.m. administration. Therefore, the i.m. administration is recommended for use in clinical practice because it is both easier to perform and provides similar plasma concentrations to the i.v. administration. However, further studies are needed to determine the clinical efficacy of TA for treatment of inflammatory disease after single and multiple dosages. 相似文献