scholarly journals Evaluation of Blueberry Juice in Mouse Azoxymethane-Induced Aberrant Crypts and Oxidative Damage

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Isela Álvarez-González ◽  
Fernando Garcia-Melo ◽  
Verónica R. Vásquez-Garzón ◽  
Saúl Villa-Treviño ◽  
E. Osiris Madrigal-Santillán ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Oral Route ◽  
Dna Oxidation ◽  
High Dose ◽  
Control Groups ◽  
Aberrant Crypts ◽  
Blueberry Juice ◽  
Number Of Factors ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Blueberry is a plant with a number of nutritional and biomedical capabilities. In the present study we initially evaluated the capacity of its juice (BJ) to inhibit the number of aberrant crypts (AC) induced with azoxymethane (AOM) in mouse. BJ was administered daily by the oral route to three groups of animals during four weeks (1.6, 4.1, and 15.0 μL/g), respectively, while AOM (10 mg/kg) was intraperitoneally injected to the mentioned groups, twice a week, in weeks two and three of the assay. We also included two control groups of mice, one administered distilled water and the other the high dose of BJ. A significant increase of AC was observed in the AOM treated animals, and a mean protection of 75.6% was determined with the two low doses of BJ tested; however, the high dose of the juice administered together with AOM increased the number of crypts more than four times the value observed in animals administered only AOM. Furthermore, we determined the antioxidant potential of BJ with anex vivoDPPH assay and found a dose-dependent decrease with a mean of 19.5%. We also determined the DNA oxidation/antioxidation by identifying 8-hydroxy-2′-deoxyguanosine adducts and found a mean decrease of 44.3% with the BJ administration with respect to the level induced by AOM. Our results show a complex differential effect of BJ related to the tested doses, opening the need to further evaluate a number of factors so as to determine the possibility of a cocarcinogenic potential.

A pilot study of interferon alfa-2a in combination with fluorouracil plus high-dose leucovorin in metastatic gastrointestinal carcinoma.

1991 ◽  
Vol 9 (10) ◽  
pp. 1811-1820 ◽  
Author(s):  
J L Grem ◽  
N McAtee ◽  
R F Murphy ◽  
F M Balis ◽  
S M Steinberg ◽  
...  
Keyword(s):  
Pilot Study ◽  
Drug Exposure ◽  
High Dose ◽  
Gastrointestinal Carcinoma ◽  
Time Curve ◽  
Recombinant Interferon ◽  
Dose Dependent Decrease ◽  
Grade 3 ◽  
The Impact ◽  
Dose Dependent

Thirty-one assessable patients with metastatic adenocarcinoma of the gastrointestinal tract were entered onto a pilot study designed to assess the impact of recombinant interferon alpha-2a (rIFN alpha-2a) on the toxicity and pharmacokinetics of fluorouracil (5-FU) and leucovorin (LV). Patients received an initial cycle of 5-FU (370 or 425 mg/m2/d) with LV (500 mg/m2/d) for 5 days. If tolerated, the patient received the same dose of 5-FU/LV for the second cycle on days 2 to 6, with rIFN alpha-2a at 5 x 10(6) or 10 x 10(6) U/m2/d on days 1 to 7, or with 3 x 10(6) U/m2/d on days 1 to 14. In 26 matched cycles, rIFN alpha-2a administration was associated with an increased incidence of dose-limiting mucositis and diarrhea and a significantly lower median platelet nadir; rIFN alpha-2a did not significantly affect the median WBC or granulocyte nadir. Dose-limiting toxicity occurred in all six patients entered at 425 mg/m2/d of 5-FU/LV within two cycles. The majority of patients treated with 370 mg/m2/d of 5-FU/LV and 10 x 10(6) U/m2/d rIFN alpha-2a experienced grade 3 to 4 mucositis and diarrhea, whereas patients receiving 3 x 10(6) and 5 x 10(6) U/m2/d rIFN alpha-2a had acceptable toxicity. Administration of rIFN alpha-2a was associated with a dose-dependent decrease in 5-FU clearance. The increase in the area under the 5-FU concentration-time curve (AUC) was 1.3-fold and 1.5-fold in patients receiving 5 x 10(6) and 10 x 10(6) U/m2/d rIFN alpha-2a, respectively. Thus, the increase in 5-FU toxicity with rIFN alpha-2a may be explained by alterations in 5-FU pharmacokinetics. In 22 patients without prior 5-FU therapy, three complete (13.6%) and seven partial (31.8%) responses were seen, for an overall response rate of 45.4% (95% confidence interval, 24.4% to 67.8%). Since the 5 x 10(6) U/m2/d dose of rIFN alpha-2a increased the 5-FU drug exposure and was associated with acceptable toxicity, we recommend its further evaluation as given on days 1 to 7 in combination with 5-FU 370 mg/m2/d, with high-dose LV given on days 2 to 6.

lmmunotoxicological Investigation of SCMF, a New Pyrethroid Pesticide in Mice

1994 ◽  
Vol 13 (5) ◽  
pp. 337-343 ◽  
Author(s):  
Olga Siroki ◽  
L. Institoris ◽  
E. Tatar ◽  
I. Desi
Keyword(s):  
Oral Treatment ◽  
Dose Range ◽  
High Dose ◽  
Experimental Conditions ◽  
Cell Content ◽  
Pyrethroid Pesticide ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Higher Doses ◽  
Femoral Bone Marrow

The toxicity of a new pyrethroid pesticide Supercypermethrin Forte (SCMF) was studied in male CFLP mice using classic toxicological (body weight, organ weights) and haematological (white blood cell count, haematocrit, nucleated cell content of femoral bone marrow) methods and immune function tests (PFC assay, DTH reaction). Four weeks of oral treatment in a 5 days per week system at doses of 1/10, 1/20, or 1/40 x LD50 did not cause evaluable changes in the measured parameters. When single calculated LD20, LD10, or LD5 doses of SCMF were administered on different days before termination to different groups of mice the two higher doses caused a time- and dose-dependent decrease in the splenic PCF number, Apart from some temporary toxic signs and an increase of haematocrit at the top dose the other examined parameters did not show evaluable changes. Under these experimental conditions toxic changes appeared only at the high dose range and, of those applied, the PFC assay proved to be the most sensitive method for detecting the toxicity of SCMF.

Oral antidiuretic therapy: studies in the diabetes insipidus rat

1982 ◽  
Vol 243 (5) ◽  
pp. R491-R499
Author(s):  
L. B. Kinter ◽  
R. Beeuwkes
Keyword(s):  
Drinking Water ◽  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Urine Osmolality ◽  
Progressive Increase ◽  
High Dose ◽  
Dose Dependent Decrease ◽  
Solute Excretion ◽  
Therapy Studies ◽  
Dose Dependent

In hypothalamic diabetes insipidus, water balance is achieved primarily through the thirst mechanism. The administration of an antidiuretic agent in the drinking water should restore the antidiuretic response to volume and osmoregulatory drive. To test this hypothesis, homozygous Brattleboro strain rats were given arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (dDAVP) in the drinking water in concentrations of 10–10,000 micrograms/l (AVP) and 5–10,000 micrograms/l (dDAVP). Oral AVP was found to be ineffective. Oral dDAVP resulted in 1) a progressive increase in dDAVP dose, from 2.3 to 2,559 micrograms.day-1.kg-1; 2) a dose-dependent increase in urine osmolality from 306 to 1,796 mosmol/kg; and 3) a dose-dependent decrease in urinary solute excretion. At each dDAVP dose level, stable physiological states were achieved within 24 h. Similar antidiuretic states were achieved when dDAVP was administered in increasing doses or when therapy was initiated at a high dose. These findings demonstrate that inclusion of an appropriate antidiuretic agent in the drinking water can restore the renal response to volume-osmoregulatory drive.

scholarly journals High-resolution positron emission microscopy of patient-derived tumor organoids

2020 ◽  
Author(s):  
Syamantak Khan ◽  
June Ho Shin ◽  
Valentina Ferri ◽  
Ning Cheng ◽  
Julia E. Noel ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Metabolic Imaging ◽  
Positron Emission ◽  
Pet Ct ◽  
Microscopy Method ◽  
Dose Dependent Decrease ◽  
Personalized Approach ◽  
Dose Dependent ◽  
Tumor Organoids ◽  
Better Than

AbstractOrganoid tumor models have found application in a growing array of cancer studies due to their ability to closely recapitulate the structural and functional characteristics of solid tumors. However, organoids are too small to be compatible with common radiological tools used in oncology clinics. Here, we present a microscopy method to image 18F-fluorodeoxyglucose in patient-derived tumor organoids with spatial resolution up to 100-fold better than that of clinical positron emission tomography (PET). When combined with brightfield imaging, this metabolic imaging approach functionally mirrors clinical PET/CT scans and provides a quantitative readout of cell glycolysis. In particular, the specific avidity of a tumor for FDG, or lack thereof, was maintained when the tumor cells were grown ex vivo as tumor organoids. In addition, cisplatin treatment caused a dose-dependent decrease in the metabolic activity of these organoids, with the exception of one patient whose tumor was also resistant to cisplatin treatment. Thus, FDG-imaging of organoids could be used to predict the response of individual patients to different treatments and provide a more personalized approach to cancer care.

scholarly journals Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Meital Cohen-Mazor ◽  
Rafi Mazor ◽  
Batya Kristal ◽  
Erik B. Kistler ◽  
Inbal Ziv ◽  
...  
Keyword(s):  
Cell Activation ◽  
Ex Vivo ◽  
Heparin Binding ◽  
Heparin Interaction ◽  
Anti Inflammatory ◽  
Dose Dependent Decrease ◽  
Blocking Antibodies ◽  
Dose Dependent ◽  
Superoxide Release

Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs), changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed bothin vitroandex vivostudies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin’s anti-inflammatory effects.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

Adenosine Diphosphate (ADP)-Induced ⍺-Granules Release from Platelets of Native Whole Blood Is Reduced by Ticlopidine but Not by Aspirin or Dipyridamole

1986 ◽  
Vol 56 (02) ◽  
pp. 147-150 ◽  
Author(s):  
V Pengo ◽  
M Boschello ◽  
A Marzari ◽  
M Baca ◽  
L Schivazappa ◽  
...  
Keyword(s):  
Whole Blood ◽  
Light Transmission ◽  
Ex Vivo ◽  
Early Stage ◽  
Shape Change ◽  
Adenosine Diphosphate ◽  
Dose Dependent ◽  
Plateletderived Growth Factor ◽  
Platelet Shape

SummaryA brief contact between native whole blood and ADP promotes a dose-dependent release of platelet a-granules without a fall in the platelet number. We assessed the “ex vivo” effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the a-granules release for an ADP stimulation of 0.4 (p <0.02), 1.2 (p <0.01) and 2 pM (p <0.01). No drug, however, completeley inhibits this early stage of platelet activation. The platelet release of α-granules may be related to platelet shape change of the light transmission aggregometer and may be important “in vivo” by enhancing platelet adhesiveness and by liberating the plateletderived growth factor.

Investigation of antiulcer activity of Pergularia extensa Linn

2020 ◽  
Vol 9 (2) ◽  
pp. 23-26
Author(s):  
Pavani C H
Keyword(s):  
Cardiac Glycosides ◽  
Methanol Extract ◽  
Methanolic Extract ◽  
Antiulcer Activity ◽  
Acute Oral Toxicity ◽  
Gastric Lesions ◽  
Oral Toxicity ◽  
Control Groups ◽  
Dose Dependent

This study was based on determination of the antiulcer activity from methanol extract was prepared by using barks of pergularia extensa linn.. Priliminary investigations showed presence of saponins, terpenes, cardiac glycosides, alkaloids and sterols. Based on OECD-423 Guidelines, the pharmacology and acute oral toxicity studies were conducted by using methanolic extract. Ulcer development was prevented by Tannins because of their vasoconstriction effects and due to protein precipitation. Similarly, the Methanolic extract of Pergularia extensa Linn shows triterpenoids and saponins. The phytoconstituents are present in the extract and these could be possible agents which are involved in order to prevent gastric lesions induced by aspirin. When compared to ulcerative control groups, this Pergularia extensa Linn., shows a dose dependent curative ratio. The extracts exhibited an inhibition percentage of 27.18, 45.47 and 61.28 at doses of 100, 200 and 400mg/kg doses respectively. 

Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products

2010 ◽  
Vol 3 (3) ◽  
pp. 1057-1064 ◽  
Author(s):  
Kinesh V P ◽  
Neelam D P ◽  
Punit B ◽  
Bhavesh S.B ◽  
Pragna K. S
Keyword(s):  
Diabetes Mellitus ◽  
Oral Delivery ◽  
Proteolytic Enzymes ◽  
Oral Route ◽  
The Body ◽  
Current Status ◽  
Intestinal Lumen ◽  
Insulin Administration ◽  
Novel Approaches ◽  
Dose Dependent

Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.

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