Multiple Approaches to Understanding the Toxic Dose

2021 ◽  
Vol 7 (4) ◽  
pp. 158-158
Author(s):  
Andrew Gow
Keyword(s):  
Toxic Dose

Liquid Chromatography Analysis of Clozapine in Rat Brain Tissue, Using its Molecularly Imprinted Polymer after Administration of Toxic Dose of Drug and Lipid Emulsion Therapy

2019 ◽  
Vol 15 (3) ◽  
pp. 251-257
Author(s):  
Bahareh Sadat Yousefsani ◽  
Seyed Ahmad Mohajeri ◽  
Mohammad Moshiri ◽  
Hossein Hosseinzadeh
Keyword(s):  
Rat Brain ◽  
Brain Tissue ◽  
Molecularly Imprinted Polymer ◽  
Lipid Emulsion ◽  
Limit Of Detection ◽  
Imprinted Polymer ◽  
Toxic Dose ◽  
Molecularly Imprinted ◽  
The Brain ◽  
Rat Brain Tissue

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

scholarly journals Herbal medicine use and its associated factors in the region of Sousse (Tunisia)

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
M Limam ◽  
J Sahli ◽  
I Khalfallah ◽  
M Mellouli ◽  
M Ghardallou ◽  
...  
Keyword(s):  
Health Care ◽  
Primary Health Care ◽  
Herbal Medicine ◽  
Medicinal Plants ◽  
Associated Factors ◽  
Medicine Use ◽  
Toxic Dose ◽  
Primary Health ◽  
Primary Health Care Centers ◽  
Health Care Centers

Abstract Background Patients use medicinal plants as the first-line treatment for many chronic and acute medical conditions. The lack of access to conventional health care, historical, cultural and economic considerations contributes to the important use of these plants. The purpose was to identify medicinal plants used by primary Health Care Centers' visitors in the region of Sousse (Tunisia) and to assess its associated factors. Methods A cross-sectional descriptive study was conducted among Primary health care centers' visitors of the region of Sousse (Tunisia) in 2018. We randomly selected 18 primary health centers and 50 participants were chosen from each center. Data were collected using a pre-tested questionnaire, filled through a direct interview with participants which explores: socio-demographic variables and medicinal plants' use (name of plants, symptoms, methods of preparation, routes of administration, plant source, tolerance and side effects). Results 900 persons were included with a female predominance (72.4%). The median age of participants was 48 years ranging from 18 to 93. 65.2% (n = 587) of them report using medicinal plants to heal. The most common sources of information were family (90.5%), beliefs and traditions (56.4%). Fifty-three (53) plants were used to treat different disorders. The most used plants are: verbena (81.6%), rosemary (53.3%), mint (52%) and thyme (45.1%). The most reported treated symptoms were: flu and gastro-intestinal disorders. Plants utilization was associated to: lower age, female gender, marital status, high level of education and social existence of protection coverage. Conclusions Plants use should be based on well-conducted scientific results specifying the mechanism of action of plants, the therapeutic and toxic dose through researches on local plants samples and extracts. Key messages It seems essential to train health professionals on herbal therapy during their studies and practice. The further step after this picture of the herbal medicine use in the Region of Sousse, is to evaluate the safety and the efficacy of their use.

scholarly journals An Orally Bioavailable (Mice) Prodrug of Glutathione

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 939
Author(s):  
Daune L. Crankshaw ◽  
Jacquie E. Briggs ◽  
Robert Vince ◽  
Herbert T. Nagasawa
Keyword(s):  
Oral Bioavailability ◽  
Toxic Dose ◽  
Mixed Disulfide ◽  
Wide Range ◽  
Orally Bioavailable

L-Cysteine-glutathione mixed disulfide (CySSG), a prodrug of glutathione (GSH), was found to be orally bioavailable in mice, and protected mice against a toxic dose of acetaminophen. If oral bioavailability can also be demonstrated in humans, a wide range of applicability for CySSG can be envisioned.

scholarly journals Acute liver injury associated with Oxyfluorfen toxicity

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110004
Author(s):  
Selladurai Pirasath ◽  
Ayshanie Gayanthika Samasundara Mudiyanselage ◽  
Manosha Harshani Seneviratne
Keyword(s):  
Sri Lanka ◽  
Liver Injury ◽  
Young Woman ◽  
Broad Spectrum ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Toxic Dose ◽  
Acute Hepatic Injury ◽  
Haem Biosynthesis ◽  
Spectrum Control

Oxyfluorfen is a phenoxyphenyl-type herbicide which is used for broad-spectrum control of broadleaf and grassy weeds. Ingestion of toxic dose of oxyfluorfen can be fatal among animals. However, toxicity to humans are rare in literature. The alterations in haem biosynthesis (anaemia) and in liver are the primary toxic effects. There are no specific antidotes and none of the current treatments have proven efficacious till date. Therefore, prevention needs to be the utmost priority, and on exposure, aggressive decontamination should be initiated. Herein, we described an oxyfluorfen toxicity with acute hepatic injury in a young woman who presented with a deliberate self-harming with an oxyfluorfen poisoning in Sri Lanka.

The Effect of Chloroquine on the Apoptosis Induced by Cisplatin in Human Gastric Cancer BGC823 Cells

2014 ◽  
Vol 926-930 ◽  
pp. 1124-1127
Author(s):  
Zhen Xun Jin ◽  
Li Li Zhang ◽  
Yan Wang ◽  
Lin Chuan Zeng ◽  
Yang Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Confocal Microscopy ◽  
Laser Scanning ◽  
Laser Scanning Confocal Microscopy ◽  
Combination Group ◽  
Human Gastric Cancer ◽  
Apoptotic Cells ◽  
Toxic Dose ◽  
Scanning Confocal Microscopy ◽  
Mtt Tests

The aim of this study is to investigate the effects and mechanism of chloroquine (CQ) on the apoptosis induced by cisplatin in human gastric cancer BGC823 cells. MTT assay was used to detect the state of cell growth. The appearances of cellular apoptosis were detected by laser scanning confocal microscopy and light microscopy. The expressions of LC3 and p62 were detected by laser scanning confocal microscopy. MTT tests showed that the non-toxic dose of CQ could increase the inhibition rate of BGC823 cells induced by cisplatin. Under the light microscope, the ratio of apoptotic cells in the group treated with non-toxic dose of CQ combined with cisplatin was higher than that in the group treated with cisplatin alone. Hoechst33342 staining showed that the ratio of apoptotic cells in the combination group was higher than that in the cisplatin group. The expression and colocalization of LC3 and p62 proteins were significantly increased in the combination group. These results indicate that CQ can enhance the cell apoptosis induced by cisplatin in BGC823 cells, which is through the inhibition of autophagy.

scholarly journals A Clinical Study of Toxication Caused by Carbamazepine Abuse in Adolescents

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Wei Xu ◽  
Yu-Lin Chen ◽  
Ying Zhao ◽  
Li-Jie Wang ◽  
Jiu-Jun Li ◽  
...  
Keyword(s):  
School Performance ◽  
Young Patients ◽  
Median Dose ◽  
Toxic Dose ◽  
Adolescent Population ◽  
Urban Rural ◽  
The Difference ◽  
Abuse Treatment ◽  
First Time ◽  
At Risk Adolescents

Carbamazepine is known to produce the side effect of euphoria. As such, it lends itself to being a drug of abuse, particularly in the adolescent population. This retrospective study evaluated carbamazepine abuse, treatment course, and associated morbidity in Chinese adolescents. The median dose of carbamazepine resulting in overdose was 2,000 mg (800–5,000). Patients were largely from urban-rural fringe areas (76.47%, 52.94%) with school performance within the last 1/3 range and (52.94%) unsupervised by parents. 35.29% experienced an obvious sense of euphoria. All patients had nervous system symptoms, 6 (35.29%) cases developed coma (GCS < 8), and 5 (29.41%) cases experienced convulsion. Four cases were treated with hemodialysis. The incidence rate in young patients with repeat carbamazepine use and without the supervision of parents was higher than that in first-time users (5/7 versus 4/10), but the difference was not significant. The toxic dose of repeat users was 3428 ± 1035 mg, significantly higher than that of 1470 ± 646 mg in first-time users (P=0.001). Carbamazepine can produce a sense of euphoria, which is more likely to lead to its abuse and overdose in adolescents. To prevent carbamazepine abuse and overdose will be critical in educating at-risk adolescents and preventing associated morbidities in the future.

scholarly journals Intraspecific variation in metal tolerance modulate competition between two marine diatoms

2021 ◽  
Author(s):  
Björn Andersson ◽  
Anna Godhe ◽  
Helena L. Filipsson ◽  
Linda Zetterholm ◽  
Lars Edler ◽  
...  
Keyword(s):  
Competitive Advantage ◽  
Dose Response ◽  
Metal Tolerance ◽  
Marine Phytoplankton ◽  
Strain Selection ◽  
Control Treatment ◽  
Toxic Stress ◽  
Marine Diatoms ◽  
Toxic Dose ◽  
Multiple Strains

AbstractDespite widespread metal pollution of coastal ecosystems, little is known of its effect on marine phytoplankton. We designed a co-cultivation experiment to test if toxic dose–response relationships can be used to predict the competitive outcome of two species under metal stress. Specifically, we took into account intraspecific strain variation and selection. We used 72 h dose–response relationships to model how silver (Ag), cadmium (Cd), and copper (Cu) affect both intraspecific strain selection and competition between taxa in two marine diatoms (Skeletonema marinoi and Thalassiosira baltica). The models were validated against 10-day co-culture experiments, using four strains per species. In the control treatment, we could predict the outcome using strain-specific growth rates, suggesting low levels of competitive interactions between the species. Our models correctly predicted which species would gain a competitive advantage under toxic stress. However, the absolute inhibition levels were confounded by the development of chronic toxic stress, resulting in a higher long-term inhibition by Cd and Cu. We failed to detect species differences in average Cu tolerance, but the model accounting for strain selection accurately predicted a competitive advantage for T. baltica. Our findings demonstrate the importance of incorporating multiple strains when determining traits and when performing microbial competition experiments.

DIGITALIS TOLERANCE IN YOUNG PUPPIES

PEDIATRICS ◽  
1970 ◽  
Vol 46 (5) ◽  
pp. 730-736
Author(s):  
Katherine H. Halloran ◽  
Steven C. Schimpff ◽  
Jean G. Nicolas ◽  
Norman S. Talner
Keyword(s):  
Blood Gases ◽  
Acid Base Balance ◽  
Acid Base ◽  
Littermate Control ◽  
Premature Ventricular Contractions ◽  
Toxic Dose ◽  
Arterial Blood ◽  
Wide Range ◽  
Base Balance ◽  
The Mean

Tolerance to acetyl strophanthidin, a rapid-acting cardiac aglycone, was determined in 28 anesthetized mongrel puppies, ages 16 to 56 days, and compared to tolerance in 16 littermate puppies in whom acute hypercapnic acidemia was produced. The tolerance was also compared to that of four adult mongrel dogs. The toxic dose was defined as the intravenous amount required to produce four consecutive premature ventricular contractions. A marked variation in the toxic dose was found in the 28 control puppies (range 83 to 353 µg/kg, mean 169 µg/kg) which could not be correlated with age, arterial blood gases or pH, serum potassium or sodium, arterial pressure, or heart rate. The toxic dose was significantly greater in the puppies than in the adult dogs, in whom the mean toxic dose was 64 µg/kg (range 50 to 89 µg/kg). A significant increase in tolerance was also observed in the puppies with hypercapnic acidemia (mean toxic dose 220 µg/kg, range 93 to 375 µg/kg) in comparison to tolerance in the control puppies and despite the wide range of tolerance, each of the puppies with hypercapnic acidemia showed greater tolerance than its littermate control puppy. Assessment of the clinical implications of these findings will require study of the effects of alterations in acid-base balance on the inotropic effect of acetyl strophanthidin in addition to the toxic electrophysiologic effects.

scholarly journals Ultra-structural and histochemical analysis of channel catfish (Ictalurus punctatus) liver treated with fumonisin B1

2008 ◽  
Vol 51 (2) ◽  
pp. 333-344 ◽  
Author(s):  
Rejane Maria Cirra Scaff ◽  
Vildes Maria Scussel
Keyword(s):  
Image Analysis ◽  
Ictalurus Punctatus ◽  
Channel Catfish ◽  
Fumonisin B1 ◽  
Electronic Microscopy ◽  
Histochemical Analysis ◽  
Toxic Dose ◽  
Apoptosis Process ◽  
Histopathological Effects ◽  
Cytoplasm Vacuolization

The histopathological effects of fumonisin B1 (FB1) injected intraperitoneally (IP), was evaluated in catfish (Ictalurus punctatus). Fishes were divided into four Groups. Groups II, III and IV were treated IP with FB1 injections of 1; 5 and 10 mg/kg bw/day, respectively, during 21 days. At the 7th, 14th and 21st day, fishes were sacrificed. The livers were hystologicaly analysed by the light and transmission electronic microscopy. Livers from the 7th day showed organelles alterations, particularly in the granular endoplasmatic reticle, mitochondria, nucleus and nucleolus mediated by FB1 doses. The occurrence of processes involved in the necrosis and apoptosis was detected. At the highest FB1 dose,the livers presented an intense response with an accentuate tissue disorganization, absence of cell limits and intense cytoplasm vacuolization. The image analysis showed the occurrence of necrosis in some areas, characterized by fully broken or swollen cells. The apoptosis was observed as the cytoplasm contraction and the chromatin formed masses concentrated in the edge of the nucleus. There was strong evidence that the numerous hepatocytes in the liver from the fishes under the toxic dose of FBs were selectively removed by the apoptosis process.

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