scholarly journals The Role of Clomipramine in Potentiating the Teratogenic Effects of Caffeine in Pregnant Rats: A Histopathological Study

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Vahid Nikoui ◽  
Sattar Ostadhadi ◽  
Nasrin Takzare ◽  
Seyyed Mohammad-Ali Nabavi ◽  
Mario Giorgi ◽  
...  
Keyword(s):  
Normal Saline ◽  
Histopathological Study ◽  
Simultaneous Administration ◽  
Teratogenic Effects ◽  
Pregnant Rats ◽  
Palate Development ◽  
Rat Fetuses ◽  
Group Control ◽  
High Doses

Since little is known about the teratogenic effects of clomipramine used concurrently with caffeine during the organogenesis period, the aim of this study was to test the teratogenic effects of a coadministration of caffeine and clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control) received 0.5 mL of normal saline. Clomipramine was injected at 40 mg/kg and 80 mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeine in doses of 60 mg/kg and 120 mg/kg, respectively. The sixth group received a combination of 40 mg/kg clomipramine and 60 mg/kg caffeine, and the seventh group was given clomipramine and caffeine at 80 mg/kg and 120 mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeine or combinations of caffeine and clomipramine showed a significant rate of cleft palate development, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (P≤0.001). This study concludes that caffeine in high doses or the simultaneous administration of caffeine and clomipramine leads to teratogenicity.

scholarly journals Teratogenic Effects of Coadministration of Fluoxetine and Olanzapine on Rat Fetuses

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Azam Bakhtiarian ◽  
Nasrin Takzare ◽  
Mehdi Sheykhi ◽  
Narges Sistany ◽  
Farahnaz Jazaeri ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Normal Saline ◽  
Concomitant Administration ◽  
Control Group ◽  
Teratogenic Effects ◽  
Pregnant Rats ◽  
Palate Development ◽  
Rat Fetuses ◽  
Significant Rate ◽  
High Doses

Objective. Depression during pregnancy is a relatively common problem. Since little is known about the teratogenic effects of concomitant administration of fluoxetine and olanzapine during the organogenesis period, the aim of the present study was to evaluate the teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses.Method. Forty-two pregnant rats were divided into seven groups, randomly. The first group received 0.5 mL of normal saline as the control. The second and third groups received fluoxetine at doses of 9 mg/kg and 18 mg/kg, respectively. Olanzapine was injected at 3 mg/kg and 6 mg/kg to the fourth and fifth groups, respectively. The sixth group received 9 mg/kg fluoxetine and 3 mg/kg olanzapine. Finally, the seventh group was administrated with fluoxetine and olanzapine at 18 mg/kg and 6 mg/kg, respectively. Drugs were injected intraperitoneally between day eight and day 15 of the pregnancy. On the 17th day of pregnancy, the fetuses were removed and micro-/macroscopically studied.Results. Fetuses of rats receiving high doses of these drugs showed a significant rate of cleft palate development, premature eyelid opening and torsion anomalies, compared to the control group (P≤0.01). It is concluded that these drugs can lead to teratogenicity, so their concomitant use during pregnancy should be avoided, or if necessary their doses must be decreased.

scholarly journals Teratogenic effects of imidacloprid in rats: mechanistic role of oxidative stress

2019 ◽  
Vol 7 (2) ◽  
pp. 35
Author(s):  
Nermeen Borai El-Borai ◽  
Seham Said Hadad ◽  
Hanem Kamal Khalifa
Keyword(s):  
Oxidative Stress ◽  
High Dose ◽  
Dependent Manner ◽  
Teratogenic Effects ◽  
Pregnant Rats ◽  
Skeletal Malformations ◽  
Fetal Malformations ◽  
High Doses ◽  
Dose Dependent

Extensive use of imidacloprid (IMI) insecticide in the agro-vet practices leads to continuous animal and human exposure. Exposure of pregnant dams to such insecticides results in fetal malformations. In the light of this, the present study was designed to investigate the teratogenic effects of two different doses of IMI and the possible mechanistic role of oxidative stress. Fifteen pregnant females were randomly divided into three equal groups and orally treated daily during organogenesis period (6-15th GD), control (distilled water), LD-IMI (45 mg/kg) and HD-IMI (90 mg/kg). All pregnant dams were exposed to caesarean section on GD 20. Exposure to IMI induced significant increase in the percentage of resorptions at high-dose with significant reduction of fetal and placental weights in a dose-dependent manner. External fetal morphological abnormalities were recorded only at high-dose while several visceral abnormalities were observed in fetuses at low- and high-doses. Significant increases in the percentages of fetal skeletal malformations were recorded only in the high-dose group. Significant changes in MDA, GSH levels and CAT activity with insignificant change in the level of H2O2 were recorded only in placentae of LD-IMI group. However, all these parameters recorded significant changes in serum of dams, placentae and liver of fetuses at high-dose. In conclusion, exposure of pregnant rats to IMI, particularly at higher-dose, during the period of organogenesis induced fetal teratogenic effects that may be related to its maternal and fetal oxidative damaging impacts.   

scholarly journals The Teratogenic Mechanism of Echinochrome as a Hypoglycemic Agent on Wistar Rats

2019 ◽  
Vol 9 (1) ◽  
pp. 79-83
Author(s):  
Ayman S. Mohamed ◽  
Eman Y. Salah EL Din ◽  
Neveen A. Farag ◽  
Abdel Rahman A. Tawfik
Keyword(s):  
Wistar Rats ◽  
Low Dose ◽  
Body Weight Gain ◽  
Control Group ◽  
High Dose ◽  
Teratogenic Effects ◽  
Pregnant Rats ◽  
Hypoglycemic Agent ◽  
Group Control ◽  
Group Control Group

Background: Echinochrome (Ech) is the active ingredient in the Histochrome drug, which possesses strong antioxidant, hypolipidemic and hypoglycemic activity. Objective: The present work aimed to characterize the malformations induced by moderate and high dose of Ech during pregnancy. Methods: In this study, eighteen (18) female pregnant rats were assigned into 3 groups (6 rats/ group); control group, low dose Ech (0.1 mg/kg) and high dose Ech (1 mg/kg). Results: The high dose of Ech caused a significant decrease in the number of embryos, uteri weight, body weight gain, placenta weight, and embryo weight and length. Also, the high dose led to a significant increase in serum AST, ALT, ALP, urea and uric acid of mothers. Conclusion: Our findings revealed the first teratogenic effects of high dose Ech. The teratogenic mechanism of Ech works through induction of the hypoglycemic condition in pregnant rats.

ʟ-Tyrosine as a Precursor of Flavonoids in Buckwheat Cotyledons

1985 ◽  
Vol 40 (3-4) ◽  
pp. 154-159 ◽  
Author(s):  
U. Margna ◽  
L. Laanest ◽  
E. Margna ◽  
T. Vainjärv
Keyword(s):  
Shikimic Acid ◽  
Incorporation Rate ◽  
Simultaneous Administration ◽  
Shikimic Acid Pathway ◽  
Acid Pathway ◽  
High Doses ◽  
Similar Decrease ◽  
Natural Precursor

Abstract Exogenous ʟ-tyrosine was incorporated 13 -14 times less effectively than exogenous L-phenylalanine into flavonoids in excised cotyledons of 3 days old buckwheat seedlings but proved to be an only 5 times poorer precursor when the experiments were carried out with 5 days old material. Simultaneous administration of ʟ-phenylalanine markedly reduced incorporation of ʟ-tyrosine into flavonoids. A similar decrease in the utilization of exogenous ʟ-tyrosine for flavonoid bio­ synthesis occurred in kinetin-treated cotyledons. However, in cotyledons treated with high doses of glyphosate, an inhibitor of the shikimic acid pathway, an increase in the formation of flavonoids from exogenously supplied ʟ-tyrosine was observed. Under all conditions the relative incorporation rate of exogenous L-tyrosine was highest for anthocyanins and lowest for C-glycosylflavones while within the latter class of compounds the luteolinic derivatives orientin and isoorientin incorporated more label than their apigeninic analogues vitexin and isovitexin. PAL and TAL activities were found to be present in the cotyledons in a ratio of 50:1. The possible role of ʟ-tyrosine as an alternative natural precursor for the biosynthesis of flavonoids and other related polyphenols is discussed.

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

The role of intracanal medicaments in inhibition of bacteria isolated from root canals of infected primary molars

2019 ◽  
Vol 14 (1) ◽  
pp. 92
Author(s):  
Dr. Maha Abdul- Kareem Mahmood ◽  
Dr. Huda Elias Ali ◽  
Dr. Haraa Khairi Abdul-Kadher
Keyword(s):  
Antimicrobial Activity ◽  
Streptococcus Mutans ◽  
Normal Saline ◽  
Root Canal ◽  
Primary Teeth ◽  
Primary Molars ◽  
Root Canals ◽  
Etiologic Agents ◽  
Micro Organisms

Microbes are considered as the primary etiologic agents in endodontic diseases.Disinfection of the root canal is obtained by the combined effect of biomechanicalpreparation, irrigation and intra canal medicament. The aim of the present study wasto assess the antimicrobial activity of intracanal medicaments (formocresol andEndosepton) against two micro organisms (Streptococcus mutans and staphylococcusaureus) isolated from 15 necrotic pulps of primary molars indicated for pulpectomyprocedure. The samples were cultured, and purified using microbiological evaluation.Broth dilution test was performed in our study by preparing test tubes containing10 ml of BHI broth (pH. 7) which then inoculated with strains of the tested bacteriaand incubated at 37 C° for 24 h. After over night incubaction, ten fold dilution weremade in test tubes containing 9 ml of normal saline by adding 1 ml of the inoculum tothe first tube . Then from dilution 10-1 , 0.1 ml of cell suspension was added to 9.9 mlof formocresol and endosepton, then 0.1 ml was taken and spread on duplicates ofBHI agar plates at different intervals and incubated aerobically for 24 h. at 37 C°.Colonies on the plates were counted after incubation and CFU/mL (colony formingunit) was calculated. Our results indicating that there were no significant differencesbetween the intracanal medicaments, but there were high significant differencesbetween the intervals time of the study. We concluded that both materials had greatantibacterial effect against the pathogens commonly isolated from necrotic pulpaltissue of primary teeth.

scholarly journals Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ariadna Recasens ◽  
Sean J. Humphrey ◽  
Michael Ellis ◽  
Monira Hoque ◽  
Ramzi H. Abbassi ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Cyclin B ◽  
Anaphase Promoting Complex ◽  
Mechanistic Studies ◽  
Glioblastoma Cells ◽  
Cycle Arrest ◽  
Dual Specificity ◽  
Rb Pathway ◽  
High Doses

AbstractBoth tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins. DYRK1A inhibition leads to the accumulation of cyclin B and activation of CDK1. Importantly, we established that the phenotypic response of glioblastoma cells to DYRK1A inhibition depends on both retinoblastoma (RB) expression and the degree of residual DYRK1A activity. Moderate DYRK1A inhibition leads to moderate cyclin B accumulation, CDK1 activation and increased proliferation in RB-deficient cells. In RB-proficient cells, cyclin B/CDK1 activation in response to DYRK1A inhibition is neutralized by the RB pathway, resulting in an unchanged proliferation rate. In contrast, complete DYRK1A inhibition with high doses of inhibitors results in massive cyclin B accumulation, saturation of CDK1 activity and cell cycle arrest, regardless of RB status. These findings provide new insights into the complexity of context-dependent DYRK1A signalling in cancer cells.

scholarly journals The Effects of N-Acetylcysteine on the Rat Mesocorticolimbic Pathway: Role of mGluR5 Receptors and Interaction with Ethanol

2021 ◽  
Vol 14 (6) ◽  
pp. 593
Author(s):  
Sandra Fernández-Rodríguez ◽  
Claudia Esposito-Zapero ◽  
Teodoro Zornoza ◽  
Ana Polache ◽  
Luis Granero ◽  
...  
Keyword(s):  
Behavioral Activation ◽  
Ethanol Administration ◽  
Metabotropic Receptors ◽  
Negative Allosteric Modulator ◽  
High Doses ◽  
Cell Expression ◽  
Mucolytic Agent ◽  
Different Doses

N-acetylcysteine (NAC) is a prodrug that is marketed as a mucolytic agent and used for the treatment of acetaminophen overdose. Over the last few decades, evidence has been gathered that suggests the potential use of NAC as a new pharmacotherapy for alcohol use disorder (AUD), although its mechanism of action is already being debated. In this paper, we set out to assess both the potential involvement of the glutamate metabotropic receptors (mGluR) in the possible dual effect of NAC administered at two different doses and NAC’s effect on ethanol-induced activation. To this aim, 30 or 120 mg/kg of NAC was intraperitoneally administered to rats with the presence or absence of the negative allosteric modulator of mGluR5 (MTEP 0.1 mg/kg). Thereafter, the cFOS IR-cell expression was analyzed. Secondly, we explored the effect of 120 mg/kg of NAC on the neurochemical and behavioral activation induced by intra-VTA ethanol administration (150 nmol). Our results showed that the high NAC dose stimulated cFOS expression in the NAcc, and that this effect was suppressed in the presence of MTEP, thus suggesting the implication of mGluR5. Additionally, high doses could attenuate the ethanol-induced increase in cFOS-expression in the NAcc, probably due to a phenomenon based on the long-term depression of the MSNs. Additional experiments are required to corroborate our hypothesis.

scholarly journals Vitamin C—Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 615
Author(s):  
Martin Doseděl ◽  
Eduard Jirkovský ◽  
Kateřina Macáková ◽  
Lenka Krčmová ◽  
Lenka Javorská ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Iron Absorption ◽  
Plasma Concentrations ◽  
Physiological Role ◽  
Renal Stones ◽  
Anti Oxidant ◽  
High Doses ◽  
Epigenetic Processes

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence—scurvy. The only clinically well-documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is relatively safe, but caution should be given to the administration of high doses, which can cause overt side effects in some susceptible patients (e.g., oxalate renal stones). Lastly, analytical methods for its determination with advantages and pitfalls are also discussed in this review.

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