Effects of cyclophosphamide treatment before implantation on the development of rat embryos after implantation

Development ◽  
1977 ◽  
Vol 41 (1) ◽  
pp. 65-78
Author(s):  
Horst Spielmann ◽  
Hans-Georg Eibs ◽  
Hans-Joachim Merker
Keyword(s):  
Early Stage ◽  
Subsequent Development ◽  
Cell Number ◽  
Pregnant Rats ◽  
Cyclophosphamide Treatment ◽  
Wet Weight ◽  
Dose Dependent Decrease ◽  
Decidual Reaction ◽  
Dose Dependent

After treatment of pregnant rats 24 h before implantation with a single injection of cyclophosphamide (20–80 mg/kg), a dose-dependent increase in resorption was observed at term but no malformed fetuses could be found. The lowest cyclophosphamide dose that caused 100 % resorption was 60 mg/kg. Somite number and wet weight indicated retardation of about 24 h during organogenesis. Determination of the time of implantation revealed that the developmental retardation in treated embryos was not due to delayed implantation. At implantation, 24 h after cyclophosphamide treatment, a significant and dose-dependent decrease of the cell number of blastocysts was found. Embryo transplantation experiments showed that early cyclophosphamide treatment interfered with the subsequent development of both the embryo and the mother. The decidual reaction seemed to be more affected by the treatment than the embryos. Most teratologists hold that mouse embryos after treatment in the preimplantation period either die before implantation or survive to term without being malformed. The present study, however, proves that the reaction of drugs at this early stage of pregnancy is more complex than is generally assumed.

Inhibitory Effects of Purple Sweet Potato Leaf Extract on the Proliferation and Lipogenesis of the 3T3-L1 Preadipocytes

2015 ◽  
Vol 43 (05) ◽  
pp. 915-925 ◽  
Author(s):  
Shou-Lun Lee ◽  
Hsien-Kuang Lee ◽  
Ting-Yu Chin ◽  
Ssu-Chieh Tu ◽  
Ming-Hsun Kuo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sweet Potato ◽  
Early Stage ◽  
Water Extract ◽  
Potato Leaf ◽  
Purple Sweet Potato ◽  
Pre Treatment ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Purple sweet potato leaves (PSPLs) are healthy vegetable that is rich in anti-oxidants. A solution of boiling water extract of PSPL (PSPLE) is believed to be able to prevent obesity and metabolic syndrome in the countryside of Taiwan, but its efficacy has not yet been verified. The purpose of this study was to investigate the possible anti-adipogenesis effect of PSPLE in vitro. PSPLE was used to treat the 3T3-L1 cells, and the effects on cell proliferation and adipogenesis were investigated. The results showed that PSPLE caused a dose-dependent decrease in the cell proliferation of 3T3-L1 preadipocytes, but did not alter the cell viability. In addition, PSPLE induced ERK inactivation in the 3T3-L1 preadipocytes. Furthermore, pre-treatment of confluent 3T3-L1 cells with PSPLE led to reduced lipid accumulation in differentiated 3T3-L1 cells. The inhibition of lipogenesis could result from the PSPLE-induced down-regulation of the expression of the C/EBPα and SREBP-1 transcription factors during 3T3-L1 adipocyte differentiation. These results suggest that PSPLE not only inhibits cell proliferation at an early stage but also inhibits adipogenesis at a later stage of the differentiation program.

Pregnancy and steroid hormones enhance the vasodilation responses to CGRP in rats

1999 ◽  
Vol 276 (1) ◽  
pp. H284-H288 ◽  
Author(s):  
P. R. R. Gangula ◽  
H. Zhao ◽  
S. Supowit ◽  
S. Wimalawansa ◽  
D. DiPette ◽  
...  
Keyword(s):  
Steroid Hormone ◽  
Sesame Oil ◽  
Pregnant Rats ◽  
Sex Steroid Hormone ◽  
Arterial Blood ◽  
Ovx Rats ◽  
Before And After ◽  
Vascular Sensitivity ◽  
Dose Dependent Decrease ◽  
Dose Dependent

We recently reported that calcitonin gene-related peptide (CGRP) reversed the hypertension induced by nitric oxide inhibition in pregnant rats and that this effect appeared to be progesterone dependent. In the present study, we examined whether the vasodilator responses to CGRP are increased during pregnancy and whether these responses are steroid hormone dependent. Three groups of ovariectomized (Ovx) rats ( n = 4–8 rats/group) were studied 3 days after daily treatment (subcutaneous injection) with progesterone (P; 2 mg/injection, twice daily for 3 days, in 0.2 ml of sesame oil), 17β-estradiol (E; 2.5 μg/injection, twice daily for 3 days, in 0.2 ml of sesame oil), or vehicle (sesame oil). A fourth group ( n = 6 rats) of pregnant rats was studied on day 19of gestation. A fifth group of adult, nonpregnant rats ( n = 6 rats), regardless of stage of estrous cycle, was also used in this study. Mean arterial blood pressure (MAP) was continuously monitored in fully awake and free-moving instrumented rats. MAP was measured before and after administration of either saline or varying bolus doses of CGRP (9–360 pmol/kg body wt). CGRP produced a dose-dependent decrease in MAP in all rats with a significant ( P < 0.05) reduction in MAP beginning with a CGRP dose of 90 pmol/kg and with maximal effects observed at 360 pmol/kg. Decreases in MAP in response to CGRP were significantly ( P < 0.05) greater in pregnant compared with nonpregnant rats. Similarly to pregnant rats, Ovx rats given both E and P treatments produced greater decreases in MAP in response to CGRP at 90, 180, and 360 pmol/kg doses compared with both ovary-intact and Ovx nonpregnant rats, which were not different from each other. In summary, these data show that 1) the hypotensive effects of CGRP are dose dependent and 2) the hypotensive effects of CGRP are enhanced during pregnancy and in Ovx rats treated with either E or P. Therefore, we suggest that the decrease in vascular tone that is seen during pregnancy may be mediated, at least in part, by a sex steroid hormone-induced increase in the vascular sensitivity to the vasodilator effects of CGRP.

scholarly journals The effect of tributyltin on human eosinophylic leukemia EoL-1 cells

2008 ◽  
Vol 13 (1) ◽  
Author(s):  
Jolanta Sroka ◽  
Przemysław Włosiak ◽  
Anna Wilk ◽  
Justyna Antonik ◽  
Jarosław Czyż ◽  
...  
Keyword(s):  
Human Blood ◽  
Human Fibroblasts ◽  
Basic Function ◽  
Organotin Compounds ◽  
Cellular Model ◽  
Dose Dependent Decrease ◽  
Dose Dependent

AbstractOrganotin compounds are chemicals that are widely used in industry and agriculture as plastic stabilizers, catalysts and biocides. Many of them, including tributyltin (TBT), have been detected in human food and, as a consequence, detectable levels have been found in human blood. As organotin compounds were shown to possess immunotoxic activity, we focused our attention on the effect of TBT on the basic determinants of the function of eosinophils, i.e. cell adhesiveness and motility. We used human eosinophylic leukemia EoL-1 cells, a common in vitro cellular model of human eosinophils. Here, we demonstrate that TBT causes a dose-dependent decrease in the viability of EoL-1 cells. When administered at sub-lethal concentrations, TBT significantly decreases the adhesion of EoL-1 cells to human fibroblasts (HSFs) and inhibits their migration on fibroblast surfaces. Since the basic function of eosinophils is to invade inflamed tissues, our results indicate that TBT, and possibly other organotin compounds, may affect major cellular properties involved in the determination of in vivo eosinophil function.

Use of a novel and highly selective oxytocin receptor antagonist to characterize uterine contractions in the rat

2007 ◽  
Vol 293 (1) ◽  
pp. R299-R305 ◽  
Author(s):  
Gerald P. McCafferty ◽  
Mark A. Pullen ◽  
Charlene Wu ◽  
Richard M. Edwards ◽  
Michael J. Allen ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Intravenous Administration ◽  
Plasma Concentrations ◽  
Oxytocin Receptor ◽  
Pregnant Rats ◽  
Uterine Contractions ◽  
Oxytocin Receptors ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Similar Affinity

Spontaneous and induced uterine contractions in the rat were found to be inhibited by a novel and selective oxytocin receptor antagonist GSK221149A (3 R,6 R)-3-Indan-2-yl-1-[(1 R)-1-(2-methyl-1,3-oxazol-4-yl)-2-morpholin-4-yl-2-oxoethyl]-6-[(1 S)-1-methylpropyl]-2,5-piperazinedione. GSK221149A displayed nanomolar affinity ( Ki = 0.65 nM) for human recombinant oxytocin receptors with >1,400-fold selectivity over human V1a, V1b, and V2 receptors. GSK221149A had similar affinity ( Ki = 4.1 nM) and selectivity for native oxytocin receptors from rat and produced a functional, competitive block of oxytocin-induced contractions in isolated rat myometrial strips with a pA2 value of 8.18. Intravenous administration of GSK221149A produced a dose-dependent decrease in oxytocin-induced uterine contractions in anesthetized rats with an ID50 = 0.27 ± 0.60 mg/kg (corresponding plasma concentrations were 88 ng/ml). Oral administration of GSK221149A (5 mg/kg) was effective in inhibiting oxytocin-induced uterine contractions after single and multiple (4-day) dosing. Spontaneous uterine contractions in late-term pregnant rats (19–21 days gestation) were significantly reduced by intravenous administration of 0.3 mg/kg of GSK221149A. These results provide further evidence that selective oxytocin receptor antagonism may offer an effective treatment for preterm labor.

The control of cell number in the lumbar spinal ganglia during the development of Xenopus laevis tadpoles

Development ◽  
1967 ◽  
Vol 17 (3) ◽  
pp. 453-471
Author(s):  
M. C. Prestige
Keyword(s):  
Dorsal Root ◽  
Early Stage ◽  
Subsequent Development ◽  
Cell Number ◽  
Limb Bud ◽  
Spinal Ganglia ◽  
Partial Removal ◽  
Motor Neurones ◽  
The Central Nervous System ◽  
Lumbar Spinal

It is the purpose of this paper to describe the development of the lumbar dorsal root ganglia after amputation of the leg. This operation can be performed at a very early stage before any connexions between the limb and the central nervous system are established. Alternatively, it can be performed at a number of later stages after the limb has been innervated. The extent of interaction can then be investigated for each stage by observing the subsequent development of the ganglia and comparing it with that of normal animals. Amputation of the limb-bud or the growing leg results in partial removal of the peripheral field for both sensory and motor neurones; the operation thus provides a means of investigating the mechanisms that control the processes of proliferation, maintenance, and degeneration of nerve cells. Detwiler and his colleagues (Detwiler, 1933) have shown that in Amblystoma loss of cells from the ganglia (hypoplasia) follows amputation, and that increase in number (hyperplasia) follows grafting of a supernumerary limb.

scholarly journals Bcl-xL–inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets

Blood ◽  
2011 ◽  
Vol 118 (6) ◽  
pp. 1663-1674 ◽  
Author(s):  
Simone M. Schoenwaelder ◽  
Kate E. Jarman ◽  
Elizabeth E. Gardiner ◽  
My Hua ◽  
Jianlin Qiao ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Early Stage ◽  
Survival Function ◽  
Bh3 Mimetics ◽  
Glycoprotein Vi ◽  
New Class ◽  
Dose Dependent Decrease ◽  
Preclinical Animal Models ◽  
Related Proteins ◽  
Dose Dependent

Abstract BH3 mimetics are a new class of proapo-ptotic anticancer agents that have shown considerable promise in preclinical animal models and early-stage human trials. These agents act by inhibiting the pro-survival function of one or more Bcl-2–related proteins. Agents that inhibit Bcl-xL induce rapid platelet death that leads to thrombocytopenia; however, their impact on the function of residual circulating platelets remains unclear. In this study, we demonstrate that the BH3 mimetics, ABT-737 or ABT-263, induce a time- and dose-dependent decrease in platelet adhesive function that correlates with ectodomain shedding of the major platelet adhesion receptors, glycoprotein Ibα and glycoprotein VI, and functional down-regulation of integrin αIIbβ3. Analysis of platelets from mice treated with higher doses of BH3 mimetics revealed the presence of a subpopulation of circulating platelets undergoing cell death that have impaired activation responses to soluble agonists. Functional analysis of platelets by intravital microscopy revealed a time-dependent defect in platelet aggregation at sites of vascular injury that correlated with an increase in tail bleeding time. Overall, these studies demonstrate that Bcl-xL–inhibitory BH3 mimetics not only induce thrombocytopenia but also a transient thrombocytopathy that can undermine the hemostatic function of platelets.

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.

BIOASSAY OF PROLACTIN

1969 ◽  
Vol 60 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Charles S. Nicoll
Keyword(s):  
Epithelial Cells ◽  
Lipid Content ◽  
Dry Weight ◽  
Fat Content ◽  
Assay Sensitivity ◽  
Mucosal Epithelium ◽  
Wet Weight ◽  
Total Dry Weight

ABSTRACT The response of the pigeon crop-sac to systemically acting prolactin (injected subcutaneously) was evaluated by measuring the wet weight of the responsive lateral lobes of the organ and by determining the dry weight of a 4 cm diameter disc of mucosal epithelium taken from one hemicrop. Of several different injection schedules tested, administration of prolactin in four daily injections was found to yield optimal responses. When compared with a graded series of prolactin doses, measurement of the mucosal dry weight proved to be a better method of response quantification than determination of the crop-sac wet weight with respect to both assay sensitivity and precision. The submucosal tissue of the crop-sac was estimated to constitute about 64 % of the total dry weight of the unstimulated organ and it was found to be relatively unresponsive to prolactin stimulation in comparison with the mucosa. The lipid content of the mucosal epithelium was determined using unstimulated crop-sacs or tissues which showed varying degrees of prolactin-induced proliferation. The fat content of the mucosal epithelial cells increased only slightly more rapidly than the dry weight or the defatted dry weight of the mucosa. Suggestions are made for the further improvement of the systemic crop-sac assay for prolactin.

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. 

Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

1988 ◽  
Vol 255 (6) ◽  
pp. R1035-R1040
Author(s):  
R. Hoo-Paris ◽  
M. L. Jourdan ◽  
L. C. Wang ◽  
R. Rajotte
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Low Temperatures ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Exogenous Insulin ◽  
Metabolic Substrate ◽  
Endogenous Insulin ◽  
Dose Dependent Decrease ◽  
Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

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