15 IN VIVO PROGESTERONE RELEASE KINETICS: A COMPARATIVE STUDY OF DIFFERENT INTRAVAGINAL DEVICES USED IN CATTLE

2011 ◽  
Vol 23 (1) ◽  
pp. 114 ◽  
Author(s):  
M. Maturana Filho ◽  
G. C. Gomes ◽  
C. V. F. Caetano ◽  
A. Kehrle ◽  
P. H. P. Miguez ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Release Kinetics ◽  
Plasma Concentrations ◽  
Fixed Time ◽  
Reproductive Efficiency ◽  
The Third ◽  
Metabolism Rate ◽  
Experimental Group ◽  
Second Use

Intravaginal progesterone (P4) releasing devices are widely used in hormonal protocols for fixed-time artificial insemination (FTAI). To reduce production cost in Brazilian farms, after first use these devices are currently reused once or twice, providing good reproductive efficiency in cattle. The aim of this study was to compare P4 plasma concentrations among time in ovariectomized cows receiving 3 different commercially available devices: Sincrogest® (SIN, 1 g of P4), Cronipres® (CRO, 1 g of P4 and 3 rings of 0,1 g of P4 for the third use) and Primer® (PRI, 1 g of P4). For each type, new (1st use, n = 2), once-used (2nd use, n = 2) and twice-used (3rd use, n = 2) devices were tested. Blood samples were collected at times 0 (before device insertion), 2, 4, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 h (Day 0 to Day 8). P4 plasma concentrations were measured by radioimmunoassay and the averages for each experimental group were submitted to analysis of variance adding repeated-measures in time factor. Comparisons were made among 3 types of device in each of 3 uses. P4 concentrations (ng mL–1) and standard deviation in the periods in which there was statistical difference (P < 0.05; a,b,cdifferent letters in the same period differ statistically) were as follows: First use: the 3 brands did not differ during the test and in Day 8 P4 levels remained near 2 ng mL–1. Second use: 2 h – SIN (3.7 ± 0.8)ab, CRO (5.4 ± 0.4)a, PRI (3 ± 0.4)b; 6 h – SIN (4 ± 0.5)a, CRO (4.9 ± 0.2)a, PRI (2.9 ± 0.3)b; and 144 h – SIN (2.2 ± 0.4)b, CRO (0.8 ± 0.3)a, PRI (1.3 ± 0.1)ab. On Day 8, Primer® and Sincrogest® P4 levels remained between 1 and 2 ng mL–1, whereas Cronipres® levels remained below 1 ng mL–1. Third use: 2 h – SIN (3.2 ± 0.04)b, CRO (7.9 ± 0.5)a, PRI (2.4 ± 0.2)b; 4 h – SIN (2.4 ± 0.4)b, CRO (5.4 ± 0.2)a, PRI (2.8 ± 0.3)b; 6 h – SIN (2.5 ± 0.8)b, CRO (7.4 ± 1.8)a, PRI (2.7 ± 0.5)b; 8 h – SIN (2.3 ± 0.2)b, CRO (5.3 ± 1.4)a, PRI (2 ± 0.1)b; 10 h – SIN (3.1 ± 0.2)b, CRO (5.5 ± 0.5)a, PRI (2.5 ± 0.2)b. 12 h – (2.7 ± 1.3)b, CRO (5.8 ± 0.6)a, PRI (2.2 ± 0,1)b; and 120 h – SIN (1.3 ± 0.2)a, CRO (0.9 ± 0.2)b, PRI (0.8 ± 0.04)b. On Day 8, all levels remained below 1 ng mL–1. In this study, P4 released concentrations differed in 3 of 15 periods in second-use device tests. In third-use device tests, Cronipres® released significantly more P4 from 2 to 12 h. It is unclear, however, if greater release of P4 in the first 24 h is advantageous, considering that Sincrogest and Primer® P4 concentrations remained above 2 ng mL–1. Additionally, it was noticed that P4 release decreased according to the number of previous uses. These findings suggest a variety of possibilities matching different device brands and different animal categories depending on animal steroid metabolism rate and consequent need for exogenous P4 supplementation. However, for such a claim, further studies on this topic are needed. Supported by FAPESP – Fundação de Amparo à Pesquisa do estado de São Paulo.

10 IN VITRO PROGESTERONE RELEASE KINETICS: A COMPARATIVE STUDY OF DIFFERENT INTRAVAGINAL DEVICES USED IN CATTLE

2011 ◽  
Vol 23 (1) ◽  
pp. 111
Author(s):  
G. C. Gomes ◽  
A. Kehrle ◽  
M. Maturana Filho ◽  
C. V. F. Caetano ◽  
J. R. V. Pimentel ◽  
...  
Keyword(s):  
Statistical Difference ◽  
Release Kinetics ◽  
In Vitro Tests ◽  
Water Mixture ◽  
The Third ◽  
Metabolism Rate ◽  
Alcohol Water ◽  
Reproduction Cost ◽  
Second Use

Since progesterone releasing devices have been used for oestrous cycle control, many studies have been done to evaluate the reduce reproduction cost. However, there are few studies about reused devices. The aim of this study was to evaluate and compare in vitro P4 releasing kinetics from 3 commercially available devices: Sincrogest® (SIN, 1 g of P4), Cronipres® (CRO, 1 g of P4 and 3 rings of 0.1 g of P4 for the third use), and Primer® (PRI, 1 g of P4). For each device, new (first use, n = 2), once-used (second use, n = 2), and twice-used (third use, n = 2) devices were tested. The tests were performed in a dissolutor sink using an alcohol/water mixture (60/40, vol/vol) as a release media. Samples were collected at 0–24 h (1P), 24–48 h (2P), 48–72 h (3P), and 72–96 h (4P). Table 1 shows the P4 amount (mg) and standard deviation in the periods in which there was statistical difference (P < 0.05; a–cdifferent letters in the same period differ statistically). The 3 brands of P4 devices differ in 2 of 4, 3 of 4, and 1 of 4 intervals for 1st-, 2nd, and 3rd-use device tests respectively. Additionally, P4 release decreased according to the number of previous uses. It is known that in vitro tests are more sensible to detect differences between devices. Nevertheless, these findings suggest the possibility of targeting different device categories for different animal categories depending on the animal steroid metabolism rate and consequent need for exogenous P4. However, for such a claim, further studies on this topic are needed. Table 1.Comparison between the 3 types in each of 3 uses Supported by FAPESP – Fundação de Amparo a Pesquisa do estado de São Paulo.

Comparison of Specific Antibody, D-Phe-Pro-Arg-CH2Cl and Aprotinin for Prevention of In Vitro Effects of Recombinant Tissue-Type Plasminogen Activator on Haemostasis Parameters

1987 ◽  
Vol 58 (03) ◽  
pp. 921-926 ◽  
Author(s):  
E Seifried ◽  
P Tanswell
Keyword(s):  
Specific Antibody ◽  
Plasma Concentrations ◽  
Fibrinolytic Therapy ◽  
Tissue Type ◽  
Control Value ◽  
Type Plasminogen Activator ◽  
In Vitro Effects ◽  
Fibrinolytic Parameters

SummaryIn vitro, concentration-dependent effects of rt-PA on a range of coagulation and fibrinolytic assays in thawed plasma samples were investigated. In absence of a fibrinolytic inhibitor, 2 μg rt-PA/ml blood (3.4 μg/ml plasma) caused prolongation of clotting time assays and decreases of plasminogen (to 44% of the control value), fibrinogen (to 27%), α2-antiplasmin (to 5%), FV (to 67%), FVIII (to 41%) and FXIII (to 16%).Of three inhibitors tested, a specific polyclonal anti-rt-PA antibody prevented interferences in all fibrinolytic and most clotting assays. D-Phe-Pro-Arg-CH2Cl (PPACK) enabled correct assays of fibrinogen and fibrinolytic parameters but interfered with coagulometric assays dependent on endogenous thrombin generation. Aprotinin was suitable only for a restricted range of both assay types.Most in vitro effects were observed only with rt-PA plasma concentrations in excess of therapeutic values. Nevertheless it is concluded that for clinical application, collection of blood samples on either specific antibody or PPACK is essential for a correct assessment of in vivo effects of rt-PA on the haemostatic system in patients undergoing fibrinolytic therapy.

A Sensitive and Facile Assay for the Measurement of Activated Protein C Activity Levels in Vivo

1993 ◽  
Vol 69 (05) ◽  
pp. 441-447 ◽  
Author(s):  
Carolyn L Orthner ◽  
Billy Kolen ◽  
William N Drohan
Keyword(s):  
Protein C ◽  
Plasma Concentrations ◽  
Limited Proteolysis ◽  
Activated Protein C ◽  
Microtiter Plate ◽  
Reversible Inhibitor ◽  
Activity Levels ◽  
Standard Curve ◽  
Agarose Beads

SummaryActivated protein C (APC) is a serine protease which plays an important role as a naturally occurring antithrombotic enzyme. APC, which is formed by thrombin-catalyzed limited proteolysis of the zymogen protein C, functions as an anticoagulant by proteolytic inactivation of the coagulation cofactors VIIIa and Va. APC is inhibited by several members of the serpin family as well a by α2-macroglobulin. APC is being developed as a therapeutic for the prevention and treatment of thrombosis. We have developed an assay to quantify circulating levels of enzymatically active APC during its administration to patients, in healthy individuals, and in various disease states. This assay utilizes an EDTA-dependent anti-protein C monoclonal antibody (Mab) 7D7B10 to capture both APC and protein C from plasma, prepared from blood collected in an anticoagulant supplemented with the reversible inhibitor p-aminobenzamidine. Mab 7D7B10-derivatized agarose beads are added to the wells of a 96-well filtration plate, equilibrated with Tris-buffered saline, and incubated for 10 min with 200 μl of plasma. After washing, APC and protein C are eluted from the immunosorbent beads with a calcium-containing buffer into the wells of a 96-well microtiter plate containing antithrombin III (ATIII) and heparin. The amidolytic activity of APC is then measured on a kinetic plate reader following the addition of L-pyroglutamyl-L-prolyl-L-arginine-p-nitroanilide (S-2366) substrate.The rate of substrate hydrolysis was proportional to APC concentration over a 200-fold concentration range (5.0 to 1,000 ng/ml) when measured continuously over a 15 to 30 min time period. The coefficient of variation was 5.9% at 35 ng/ml and 8.8% at 350 ng/ml APC. The sensitivity of the assay could be increased by measuring the amount of color produced after longer incubation times in the endpoint mode. The measured APC activity levels were little affected by varying protein C or prothrombin over the extremes of 0 to 150% of normal plasma concentrations. By constructing the standard curve in protein C-deficient plasma, the concentration of APC activity in normal pooled plasma was determined to be 2.8 ng/ml (45 pM), which represents 0.08% of the protein C concentration. The assay was approximately 50-fold more sensitive than the identical assay, but using Mab-coated microtiter wells rather than immunosorbent beads as the capture step.

The Spectrum of von Willebrand’s Disease

1967 ◽  
Vol 18 (01/02) ◽  
pp. 040-056 ◽  
Author(s):  
E. J Walter Bowie ◽  
P Didisheim ◽  
J. H Thompson ◽  
C. A Owen
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Severe Bleeding ◽  
Platelet Adhesiveness ◽  
Platelet Activity ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
The Third ◽  
Generation Test

SummaryPatients (from 5 kindreds) with variants of von Willebrand’s disease are described. In one kindred the depression of factor VIII was moderate (20 to 40% of normal) and transfusion of 500 ml of normal plasma led to an increase higher than anticipated and to an almost normal level of factor VIII 17 to 24 hrs later. This represents the usual type of von Willebrand’s disease.In the second kindred the concentration of factor VIII was less than 2 % of normal in the son and daughter, who had severe bleeding and hemarthroses.The third kindred was characterized by reduction of factor VIII and a long bleeding time as well as by a serum defect in the thromboplastin-generation test comparable to that seen in patients with hemophilia B, yet with normal levels of factors IX, X, and VII. The severity of the serum defect, the positive result with the Rumpel-Leede test, and the reduced platelet activity in the thromboplastin-generation test are all compatible with the diagnosis of thrombopathy or ‘‘thrombopathic hemophilia.” In two other kindreds, one patient had a long bleeding time and normal levels of factor VIII and another had a normal bleeding time and decrease of factor VIII. The last patient had the type of response to transfusion usually seen in von Willebrand’s disease.In four kindreds, platelet adhesiveness in vivo was found to be strikingly abnormal (virtually absent).It would appear, therefore, that von Willebrand’s disease forms a spectrum, and whether the kindreds reported simply reflect variations of a single genetic disease state or represent separate entities will be answered only by clarification of the underlying etiology of that disease.

An in vivo Model for the Assessment of Acute Fibrinolytic Capacity of the Endothelium

1997 ◽  
Vol 78 (04) ◽  
pp. 1242-1248 ◽  
Author(s):  
David E Newby ◽  
Robert A Wright ◽  
Christopher A Ludlam ◽  
Keith A A Fox ◽  
Nicholas A Boon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Plasma Concentrations ◽  
In Vivo Model ◽  
Forearm Circulation ◽  
Von Willebrand ◽  
Local Release ◽  
Willebrand Factor

SummaryThe effects on blood flow and plasma fibrinolytic and coagulation parameters of intraarterial substance P, an endothelium dependent vasodilator, and sodium nitroprusside, a control endothelium independent vasodilator, were studied in the human forearm circulation. At subsystemic locally active doses, both substance P (2-8 pmol/min) and sodium nitroprusside (2-8 μg/min) caused dose-dependent vasodilatation (p <0.001 for both) without affecting plasma concentrations of PAI-1, von Willebrand factor antigen or factor VIII:C activity. Substance P caused local increases in t-PA antigen and activity (p <0.001) in the infused arm while sodium nitroprusside did not. At higher doses, substance P increased blood flow and t-PA concentrations in the noninfused arm. We conclude that brief, locally active and subsystemic infusions of intraarterial substance P cause a rapid and substantial local release of t-PA which appear to act via a flow and nitric oxide independent mechanism. This model should provide a useful and selective method of assessing the in vivo capacity of the forearm endothelium to release t-PA acutely.

Аpplying of high-frequency monopolar diathermocoagulation in the treatment of chronic pulpitis

2020 ◽  
Vol 1 (12) ◽  
pp. 40-42
Author(s):  
F. Yu. Daurova ◽  
D. I. Tomaeva ◽  
S. V. Podkopaeva ◽  
Yu. A. Taptun
Keyword(s):  
Root Canal ◽  
High Frequency ◽  
Antibacterial Effect ◽  
Comparison Group ◽  
Poor Quality ◽  
Endodontic Treatment ◽  
Root Canals ◽  
The Third ◽  
Before And After

Relevance: the reason for the development of complications in endodontic treatment is poor-quality instrumental treatment root canals.Aims: a study of the animicrobial action and clinical efficacy of high-frequency monopolar diathermocoagulation in the treatment of chronic forms of pulpitis.Materials and methods: 102 patients with various chronic forms of pulpitis were divided into three groups of 34 patients each. In the first two groups, high-frequency monopolar diathermocoagulation was used in endodontic treatment in different modes. In the third group, endodontic treatment was carried out without the use of diathermocoagulation (comparison group). The root canal microflora in chronic pulpitis in vivo was studied twice-before and after diathermocoagulation.Results: it was established that high-frequency monopolar diathermocoagulation in the effect mode is 3, power is 4 (4.1 W) and effect is 4, power is 4 (5.4 W) with an exposure time of 3 seconds, it has a pronounced antibacterial effect on all presented pathogenic microflora obtained from the root canals of the teeth.

THE EFFECT OF APPLYING DEMONSTRATION METHOD ON STUDENTS’ ACHIEVEMENT IN SPEAKING SKILL AT THE THIRD GRADE OF SMK PAB 3 MEDAN ESTATE

2015 ◽  
Vol 4 (2) ◽  
Author(s):  
Meryanti Napitupulu And Anni Holila Pulungan
Keyword(s):  
High School ◽  
Control Group ◽  
Vocational High School ◽  
Control Groups ◽  
Speaking Test ◽  
The Third ◽  
Speaking Skill ◽  
The Subject ◽  
And Control ◽  
Experimental Group

This study was conducted as an attempt to discover the effect of applying Demonstration Method on students’ achievement in speaking skill. It was an experimental research. The subject was students of Grade XII, Vocational High School (Sekolah Menengah Kejuruan: SMK), which consisted of 79 students. The research was divided into two groups: experimental and control groups. The instrument used to collect the data was speaking test. To obtain the reliability of the test, the writer applied Kuder Richardson 21 formula. The result of the reliability was 0.7, and it was found that the test was reliable. The data were analyzed by using t-test formula. The analysis showed that the scores of the students in the experimental group were significantly higher than the scores of the students in the control group at the level of significant m = 0.05 with the degree of freedom (df) 77, t-observed value 8.9 > t-table value 1.99. The findings indicate that using Demonstration Method significantly affected the students’ achievement in speaking skill. So, English teachers are suggested to use Demonstration Method in order to improve students’ achievement in speaking skill.

Effect of recombinant bovine somatotropin on pregnancy rates of Nellore cows resynchronized with the use of new DIB and third use, and inseminated at fixed-time

2015 ◽  
Vol 4 (1) ◽  
pp. 356-362
Author(s):  
Josemara Silva Santos ◽  
Tania Cavalcante ◽  
Francisca Elda Ferreira Dias ◽  
Domenica Palomaris Mariano de Souza ◽  
Alencariano J.S. Falcão ◽  
...  
Keyword(s):  
Artificial Insemination ◽  
Linear Models ◽  
Plasma Concentrations ◽  
Fixed Time ◽  
Estradiol Benzoate ◽  
Pregnancy Rates ◽  
Recombinant Bovine Somatotropin ◽  
Equine Chorionic Gonadotropin ◽  
Rectal Palpation ◽  
Intravaginal Device

The objective of the experiment was to evaluate the effects of recombinant bovine somatropin (rbST), and the reuse of the progesterone (P4) releasing devices in resynchronization, on the pregnancy rates of Nellore cows submitted to fixed-time artificial insemination. A group of 123 multiparae Nellore cows, was submitted to a resynchronization protocol: on day 0 a Bovine Intravaginal Device (DIB® ) with 1,0g of P4 was implanted, associated with intramuscular administration of 2,0mg of estradiol benzoate (IM); on day 8 DIB was removed; and 1,0mg of estradiol cypionate, 0,15mg of prostaglandin F2? and 300 UI of equine chorionic gonadotropin were administered; on day 10, fixed-time artificial insemination was conducted (FTAI). The cows were randomized into G1 (n=12) – without rbST / with used Bovine Intravaginal Device, G2 (n=50) – without rbST / with new DIB, G3 (n=11) - with rbST / with used DIB and G4 (n=50) – with rbST/ with new DIB. rbST was introduced on the eighth day of the protocol. Sixty days after TAI, pregnancy diagnoses were conducted, via rectal palpation. Blood samples were taken on day 0, 8 and 10 of the protocol, in order to assess P4 plasma concentrations. Pregnancy rates were statistically evaluated through Generalized Linear Models Theory and their significance was tested with Analysis of Deviance. Pregnancy rates were 58%, 40%, 81% and 48% for G1, G2, G3 and G4, respectively, with significant statistical difference for G3. Plasma concentrations of P4 were not statistically different among groups, or collections. In view of the results obtained, we concluded that the administration of rbST in association with P4 DIB, used for the third time, improves pregnancy rates. Estrus resynchronization and re-insemination positively impacted pregnancy rates.

Utilizing ICG Spectroscopical Properties for Real-Time Nanoparticle Release Quantification In vitro and In vivo in Imaging Setups

2020 ◽  
Vol 26 (31) ◽  
pp. 3828-3833 ◽  
Author(s):  
Tuula Peñate-Medina ◽  
Eike Kraas ◽  
Kunliang Luo ◽  
Jana Humbert ◽  
Hanwen Zhu ◽  
...  
Keyword(s):  
Release Kinetics ◽  
Pure Water ◽  
Squamous Carcinoma ◽  
Peak Shift ◽  
Intensity Increase ◽  
Nude Mouse Model ◽  
Absorption And Emission ◽  
Squamous Carcinoma Cells

Background: Nanoparticle imaging and tracking the release of the loaded material from the nanoparticle system have attracted significant attention in recent years. If the release of the loaded molecules could be monitored reliably in vivo, it would speed up the development of drug delivery systems remarkably. Methods: Here, we test a system that uses indocyanine green (ICG) as a fluorescent agent for studying release kinetics in vitro and in vivo from the lipid iron nanoparticle delivery system. The ICG spectral properties like its concentration dependence, sensitivity and the fluctuation of the absorption and emission wavelengths can be utilized for gathering information about the change of the ICG surrounding. Results: We have found that the absorption, fluorescence, and photoacoustic spectra of ICG in lipid iron nanoparticles differ from the spectra of ICG in pure water and plasma. We followed the ICG containing liposomal nanoparticle uptake into squamous carcinoma cells (SCC) by fluorescence microscopy and the in vivo uptake into SCC tumors in an orthotopic xenograft nude mouse model under a surgical microscope. Conclusion: Absorption and emission properties of ICG in the different solvent environment, like in plasma and human serum albumin, differ from those in aqueous solution. Photoacoustic spectral imaging confirmed a peak shift towards longer wavelengths and an intensity increase of ICG when bound to the lipids. The SCC cells showed that the ICG containing liposomes bind to the cell surface but are not internalized in the SCC-9 cells after 60 minutes of incubation. We also showed here that ICG containing liposomal nanoparticles can be traced under a surgical camera in vivo in orthotopic SCC xenografts in mice.

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

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