Lobeline shows a specific antiaggressive effect after repeated administration

2000 ◽  
Author(s):  
M. C. Oterino ◽  
I. Moragrega ◽  
P. Vicens ◽  
M. C. Carrasco ◽  
R. Redolat ◽  
...  
Keyword(s):  
Repeated Administration

Nucleolar Segregation and Chronic Methanol Intoxication

1969 ◽  
Vol 27 ◽  
pp. 360-361
Author(s):  
Julio H. Garcia ◽  
Janice P. Van Zandt
Keyword(s):  
Body Weight ◽  
Methyl Alcohol ◽  
Rhesus Monkeys ◽  
Repeated Administration ◽  
Serum Levels ◽  
Methanol Intoxication ◽  
Intragastric Tube ◽  
Nucleolar Segregation

Repeated administration of methyl alcohol to Rhesus monkeys (Maccaca mulata) by intragastric tube resulted in ultrastructural abnormalities of hepatocytes, which persisted in one animal twelve weeks after discontinuation of the methyl alcohol regime. With dosages ranging between 3.0 to 6.0 gms. of methanol per kg. of body weight, the serum levels attained within a few hours averaged approximately 475 mg. per cent.

HES 200/0.5 Is not HES 200/0.5

1995 ◽  
Vol 74 (06) ◽  
pp. 1452-1456 ◽  
Author(s):  
Johannes Treib ◽  
Anton Haass ◽  
Gerhard Pindur ◽  
Ulrich T Seyfert ◽  
Wolfgang Treib ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hydroxyethyl Starch ◽  
Clinical Relevance ◽  
Dilution Effect ◽  
Repeated Administration ◽  
Plasma Viscosity ◽  
Degree Of Substitution ◽  
Pronounced Increase ◽  
Large Molecules ◽  
Mean Molecular Weight

SummaryThe plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch.10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7.After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (p<0.01). The larger C2/C6 ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in turn led to a higher increase in serum concentration during the therapy (14.7 vs.8.6 mg/ml). Hematocrit was lowered more (-30,5 vs. -23,5%) and plasma viscosity was increased more. There was also a more pronounced increase in partial thromboplastin time (+30% vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex (p <0.01), which exceeded the dilution effect.The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.

Intoxication with Phenprocoumon (Marcoumar) Pharmacokinetics and Side Effects

1969 ◽  
Vol 21 (02) ◽  
pp. 320-324 ◽  
Author(s):  
K Seiler ◽  
F Duckert
Keyword(s):  
Plasma Concentration ◽  
Side Effects ◽  
Half Life ◽  
Plasma Proteins ◽  
Repeated Administration ◽  
High Plasma ◽  
Vitamin K1 ◽  
Clotting Factors ◽  
Therapeutic Concentration ◽  
High Plasma Concentration

SummaryA case of severe Marcoumar intoxication is described. Eleven hours after the intake a plasma concentration of 15.75 µg/ml was found which corresponds approximately to the 5-fold therapeutic concentration. Repeated administration of vitamin K1 made it possible to avoid extreme lowering of the activity of the clotting factors II, VII and X and to prevent bleeding. Side effects were not observed. The biologic half-life of Phenprocoumon has been found to be shortened at high plasma concentration (3.7 instead of 5.9 days). It is probable that in extreme concentration the drug is less strongly bound to the plasma proteins.

Lauric Acid-Induced Thrombocytopenia and Thrombosis in Rabbits

1967 ◽  
Vol 18 (01/02) ◽  
pp. 057-065 ◽  
Author(s):  
G Zbinden
Keyword(s):  
Acid Solution ◽  
Intravenous Injection ◽  
Lauric Acid ◽  
Repeated Administration ◽  
Intravenous Dose ◽  
Acid Injection ◽  
Small Doses ◽  
High Doses

SummaryIntravenous injection of 0.5% lauric acid solution into rabbits caused moderate to marked thrombocytopenia. With small doses (2.5 mg/kg) this thrombocyte decrease was reversible and microscopically demonstrable thrombosis in the lungs was only seen or suspected in a small number of rabbits 10 to 30 min after lauric acid injection. High doses were followed by partly reversible thrombocytopenia and by moderate to marked, sometimes lethal, thrombosis in the lungs still demonstrable 24 hrs after injection. Repeated administration of small doses of lauric acid did not lead to a depletion of the circulating thrombocytes. Thrombocytopenic response, however, appeared to be less pronounced after the second and subsequent injections. Studies with Cr51-labeled platelets indicate that during the reversible thrombocytopenia following a small intravenous dose of lauric acid platelets are retained in various organs, particularly the lungs.

An Heuristic for the Construction of Alternative Test Forms for the Zahlen-Verbindungs-Test

1996 ◽  
Vol 82 (1) ◽  
pp. 147-152 ◽  
Author(s):  
Douglas Vickers ◽  
Charles Pearce
Keyword(s):  
Repeated Administration ◽  
Systematic Investigation ◽  
Analytical Problem ◽  
Cognitive Efficiency ◽  
Basic Reason ◽  
Trail Making ◽  
Alternative Test

Trail-making tests such as Oswald and Roth's 1987 Zahlen-Verbindungs-Test offer sensitive and reliable indicators of cognitive efficiency that are also simple, inexpensive, and quick to administer. A disadvantage is that there exist only a limited number of test forms so the scope for repeated administration and systematic investigation is restricted. The basic reason is that the principled generation of such pathways remains an unsolved analytical problem. In this note we propose an heuristic stratagem for the generation of alternative test forms for the Zahlen-Verbindungs-Test.

Formulation, Development and Characterization of Floating Beads of Diltiazem Hydrochloride

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Anamika Saxena Saxena ◽  
Santosh Kitawat ◽  
Kalpesh Gaur ◽  
Virendra Singh
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery Systems ◽  
Entrapment Efficiency ◽  
Repeated Administration ◽  
Alginate Beads ◽  
Delivery Systems ◽  
Sem Analysis ◽  
Formulation Development

The main goal of any drug delivery system is to achieve desired concentration of the drug in blood or tissue, which is therapeutically effective and nontoxic for a prolonged period. Various attempts have been made to develop gastroretentive delivery systems such as high density system, swelling, floating system. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. Gastric emptying is a complex process and makes in vivo performance of the drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 hours. The floating or hydrodynamically controlled drug delivery systems are useful in such application. Background of the research: Diltiazem HCL (DTZ), has short biological half life of 3-4 h, requires rather high frequency of administration. Due to repeated administration there may be chances of patient incompliance and toxicity problems. Objective: The objective of study was to develop sustained release alginate beads of DTZ for reduction in dosing frequency, high bioavailability and better patient compliance. Methodology: Five formulations prepared by using different drug to polymer ratios, were evaluated for relevant parameters and compared. Alginate beads were prepared by ionotropic external gelation technique using CaCl2 as cross linking agent. Prepared beads were evaluated for % yield, entrapment efficiency, swelling index in 0.1N HCL, drug release study and SEM analysis. In order to improve %EE and drug release, LMP and sunflower oil were used as copolymers along with sodium alginate.

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

scholarly journals Acupuncture Alleviates Anxiety and 22-kHz Ultrasonic Vocalizations in Rats Subjected to Repeated Alcohol Administration by Modulating the Brain-Derived Neurotrophic Factor/Corticotropin-Releasing Hormone Signaling Pathway

2021 ◽  
Vol 22 (8) ◽  
pp. 4037
Author(s):  
Su Yeon Seo ◽  
Se Kyun Bang ◽  
Suk Yun Kang ◽  
Seong Jin Cho ◽  
Kwang Ho Choi ◽  
...  
Keyword(s):  
Negative Emotions ◽  
Acupuncture Point ◽  
Repeated Administration ◽  
Ultrasonic Vocalizations ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Alcohol Administration ◽  
Heart Meridian ◽  
Mature Brain ◽  
Neurotropic Factor

The Shenmen point (acupuncture point heart 7: HT7), located in the heart meridian, is frequently used to treat mental disorders, including drug addiction, anxiety, and depression. This study aimed to determine how HT7 regulates anxiety and negative emotions caused by repeated alcohol administration, focusing on the amygdala and paraventricular nucleus (PVN). Repeated administration of alcohol (ETOH; 2 g/kg, i.p. injection, 16% v/v) for 14 days increased the corticosterone (CORT) levels, and HT7 stimulation reduced the plasma CORT levels. HT7 stimulation mitigated anxiety-like behaviors and reduced 22-kHz ultrasonic vocalizations in rats receiving repeated ETOH injections. HT7 stimulation increased the amygdala expression of mature brain-derived neurotropic factor (mBDNF) and phosphorylated tropomyosin receptor kinase B (pTrkB) and decreased the PVN corticotropin-releasing hormone (CRH) expression. Amygdala microinjections of the TrkB antagonist ANA-12 (0.1 pmol/1 μL) reversed the increase in PVN CRH levels. The reduced PVN CRH levels were regulated by CRH-expressing neurons in the amygdala, and the increased amygdala CRH levels were affected by the HT7-stimulation induced increases in mBDNF. HT7 stimulation alleviates increased stress hormone levels and mitigates anxiety and negative emotions caused by repeated ETOH administration. These results provide scientific support for the clinical use of acupuncture to treat various alcoholism-induced diseases.

scholarly journals Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats

2021 ◽  
Vol 14 (2) ◽  
pp. 97
Author(s):  
Joana Barbosa ◽  
Juliana Faria ◽  
Fernanda Garcez ◽  
Sandra Leal ◽  
Luís Pedro Afonso ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Wistar Rats ◽  
Brain Cortex ◽  
Dose Range ◽  
Fibrous Tissue ◽  
Lactate Concentration ◽  
Repeated Administration ◽  
Serum Lactate Dehydrogenase ◽  
Prescription Opioids ◽  
Therapeutic Doses

Tramadol and tapentadol, two structurally related synthetic opioid analgesics, are widely prescribed due to the enhanced therapeutic profiles resulting from the synergistic combination between μ-opioid receptor (MOR) activation and monoamine reuptake inhibition. However, the number of adverse reactions has been growing along with their increasing use and misuse. The potential toxicological mechanisms for these drugs are not completely understood, especially for tapentadol, owing to its shorter market history. Therefore, in the present study, we aimed to comparatively assess the putative lung, cardiac, and brain cortex toxicological damage elicited by the repeated exposure to therapeutic doses of both prescription opioids. To this purpose, male Wistar rats were intraperitoneally injected with single daily doses of 10, 25, and 50 mg/kg tramadol or tapentadol, corresponding to a standard analgesic dose, an intermediate dose, and the maximum recommended daily dose, respectively, for 14 consecutive days. Such treatment was found to lead mainly to lipid peroxidation and inflammation in lung and brain cortex tissues, as shown through augmented thiobarbituric acid reactive substances (TBARS), as well as to increased serum inflammation biomarkers, such as C reactive protein (CRP) and tumor necrosis factor-α (TNF-α). Cardiomyocyte integrity was also shown to be affected, since both opioids incremented serum lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) activities, while tapentadol was associated with increased serum creatine kinase muscle brain (CK-MB) isoform activity. In turn, the analysis of metabolic parameters in brain cortex tissue revealed increased lactate concentration upon exposure to both drugs, as well as augmented LDH and creatine kinase (CK) activities following tapentadol treatment. In addition, pneumo- and cardiotoxicity biomarkers were quantified at the gene level, while neurotoxicity biomarkers were quantified both at the gene and protein levels; changes in their expression correlate with the oxidative stress, inflammatory, metabolic, and histopathological changes that were detected. Hematoxylin and eosin (H & E) staining revealed several histopathological alterations, including alveolar collapse and destruction in lung sections, inflammatory infiltrates, altered cardiomyocytes and loss of striation in heart sections, degenerated neurons, and accumulation of glial and microglial cells in brain cortex sections. In turn, Masson’s trichrome staining confirmed fibrous tissue deposition in cardiac tissue. Taken as a whole, these results show that the repeated administration of both prescription opioids extends the dose range for which toxicological injury is observed to lower therapeutic doses. They also reinforce previous assumptions that tramadol and tapentadol are not devoid of toxicological risk even at clinical doses.

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