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Archives of Razi Institute Apr 2022The current study aimed to investigate the neuropharmacological properties of ethanol, acetone, and ethyl acetate leaf extracts of () in mouse models. The...
The current study aimed to investigate the neuropharmacological properties of ethanol, acetone, and ethyl acetate leaf extracts of () in mouse models. The neuropharmacological properties of this plant were studied on Swiss albino mice at dosages of 50, 100, and 200 mg/kg body weight in thiopental sodium-induced sleeping time test, and at dosages of 100 and 200 mg/kg body weight in other tests. The extracts caused a marked reduction in the initiation and sleep length (<0.05) in studies on thiopental sodium-induced sleeping time at dosages of 100 and 200 mg/kg and a significant decrease (<0.05) was found in terms of unconstrained locomotor and explorative activities in both hole crossing and open field tests at dosages of 100 and 200 mg/kg. Furthermore, the extracts increased sleeping time with a dosage-dependent onset of action. The hole-board test extracts also reduced the number of head dips at dosages of 100 and 200 mg/kg (<0.05). It was found in this study that had the best neuropharmacological properties at a dosage of 200 ml/kg. Our findings also showed that all of the extracts from were experimentally active in an model. The study results suggested that the leaves had strong anti-depressant and hypnotic CNS properties that might be exploited for neuropharmacological adjuvant therapy in conventional medicine. However, pharmacological studies are warranted to explore the active substances and the mode of action.
Topics: Mice; Animals; Rubiaceae; Plant Extracts; Thiopental; Acetone; Behavior, Animal; Hypnotics and Sedatives; Ethanol; Body Weight
PubMed: 36284956
DOI: 10.22092/ARI.2021.356880.1937 -
Experimental and Clinical... Jun 2007Tacrolimus is an effective immunosuppressant, safely administered in clinical practice by monitoring blood levels. In experimental transplants, many dosage regimens have...
OBJECTIVES
Tacrolimus is an effective immunosuppressant, safely administered in clinical practice by monitoring blood levels. In experimental transplants, many dosage regimens have been reported, often without such determinations. Anorexia and organ toxicity commonly occur. We report the toxic effects of tacrolimus in rabbits receiving intramuscular injections (1 mg/kg/d) and the subsequent dosage modifications that resulted in improved animal survival without toxic effects.
MATERIALS AND METHODS
To obtain nontoxic drug concentrations in the blood, 3 dosage regimens were required. Drug concentrations were targeted using therapeutic human values as a guide (range, 5-20 ng/mL). First, a group of 12 Dutch-Belted rabbits received vascularized femoral allografts and were treated with intramuscular dosages of tacrolimus (1 mg/kg/d) for 14 days. Subsequently, dosage reductions in 10 more rabbits, to 0.2 mg/kg/d for 14 days, were necessary. Finally, another group of 20 rabbits was treated with 0.08 mg/kg for 3 days, and then every other day thereafter. Weight loss > 30%, cardiopulmonary failure, and/or creatinine levels > 221 micromol/L were the criteria approved by our local Institutional Animal Care and Use Committee for euthanizing the animals. Treated animals were compared with 20 nonimmunosuppressed controls that underwent the same operation.
RESULTS
At an intramuscular dosage of 1 mg/kg/d, the mean tacrolimus blood level was 90.7 ng/mL. Ten of the 12 animals in the original group died or required euthanasia. At necropsy, renal failure, cardiac abnormalities, and pulmonary edema were found. The tacrolimus dosage of 0.2 mg/kg/d produced a mean tacrolimus blood level of 17.6 ng/mL; however, 8 of the subsequent 10 rabbits died when given this dosage. Ultimately, the 0.08 mg/kg regimen in 20 rabbits permitted survival of 18 animals with a mean tacrolimus blood level of 6.8 ng/mL. None of 20 nonimmunosuppressed controls died after surgery.
CONCLUSIONS
For successful immunosuppression, Dutch-Belted rabbits require intramuscular tacrolimus dosages lower those required in other rabbit breeds. This has not been reported previously. The 0.08 mg/kg/d dosage combined with intermittent drug level monitoring permits survival without significant complications.
Topics: Animals; Dose-Response Relationship, Drug; Femur; Graft Survival; Immunosuppressive Agents; Injections, Intramuscular; Mortality; Rabbits; Species Specificity; Survival Analysis; Tacrolimus
PubMed: 17617048
DOI: No ID Found -
The Cochrane Database of Systematic... 2003Methadone maintenance treatment (MMT) is a long term opioid replacement therapy, recognised as effective in the management of opioid dependence. Even if MMT at high... (Review)
Review
BACKGROUND
Methadone maintenance treatment (MMT) is a long term opioid replacement therapy, recognised as effective in the management of opioid dependence. Even if MMT at high dosage is recommended as therapy for reducing illicit opioid use and promoting longer retention in treatment, at present day "the organisation and regulation of the methadone maintenance treatment varies widely".
OBJECTIVES
To evaluate the efficacy of different dosages of MMT for opioid dependence in modifying health and social outcomes and in promoting patients' familial, occupational and relational functioning.
SEARCH STRATEGY
The following sources were scanned: - MEDLINE (OVID 1966-2001)- EMBASE (1988-2001)- ERIC (1988-2001)- Psychinfo (1947-2001)- Cochrane Controlled Trials Register (CCTR) (1947-2001)- Register of the Cochrane Drug and Alcohol Group (CDAG) (1947-2001)The CDAG search strategy was applied together with a specific MESH strategy. Further studies were searched through: letters to the authors of selected trials or to experts in order to obtain unpublished data. check of references of relevant reviews.
SELECTION CRITERIA
Randomised Controlled Trials (RCT) and Controlled Prospective Studies (CPS) evaluating methadone maintenance at different dosages in the management of opioid dependence were included in the review. Non-randomised trials were included when proper adjustment for confounding factors was performed at the analysis stage.
DATA COLLECTION AND ANALYSIS
Extraction of data was performed separately by two reviewers. Discrepancies were resolved by a third reviewer. RevMan software was used for analysis. Quality assessments of the methodology of studies were carried out using CDAG checklist.
MAIN RESULTS
22 studies were excluded from the review. 21 studies were included; of them, 11 were RCTs with 2279 people randomised and 10 were CPSs with 3715 people followed-up.
OUTCOMES
Retention rate - RCTs: High vs low doses at shorter follow-ups: RR=1.36 [1.13,1.63], and at longer ones: RR=1.62 [0.95,2.77]. Opioid use (self reported), times/w - RCTs: high vs low doses WMD= -2.00 [-4.77,0.77] high vs middle doses WMD= -1.89[-3.43, -0.35] Opioid abstinence, (urine based) at >3-4 w - RCTs: high vs low ones: RR=1.59 [1.16,2.18] high vs middle doses RR=1.51[0.63,3.61] Cocaine abstinence (urine based) at >3-4 w - RCTs: high vs low doses RR=1.81 [1.15,2.85]Overdose mortality - CPSs: high dose vs low dose at 6 years follow up: RR=0.29 [0.02-5.34] high dose vs middle dose at 6 years follow up: RR=0.38 [0.02-9.34] middle dose vs low dose at 6 years follow up: RR=0.57 [0.06-5.06]
REVIEWER'S CONCLUSIONS
Methadone dosages ranging from 60 to 100 mg/day are more effective than lower dosages in retaining patients and in reducing use of heroin and cocaine during treatment. To find the optimal dose is a clinical ability, but clinician must consider these conclusions in treatment strategies.
Topics: Controlled Clinical Trials as Topic; Humans; Methadone; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic
PubMed: 12917925
DOI: 10.1002/14651858.CD002208 -
Pharmacology, Biochemistry, and Behavior Feb 1976The ability of the intravenous administration of mazindol (SaH 42-548) to act as a reinforcer in monkeys previously conditioned to self-administer cocaine was...
The ability of the intravenous administration of mazindol (SaH 42-548) to act as a reinforcer in monkeys previously conditioned to self-administer cocaine was ascertained. Unit dosages i.e. dosage per injection, of 50 and 100 mug/kg resulted in self-administration rates significantly greater than that which occurred with saline. An inverse relationship existed between unit dosage and frequency of self-administration over the unit dosage range 50-200 mug/kg. The total mazindol dosage self-administration per session was however independent of unit dosage. Approximately 2-3 mg/kg was self-administered by each animal during a 4 hr session at each of the 3 unit dosages. This tends to indicate that the 200 mug/kg unit dosage was also reinforcing even though the self-administration rate was similar to that of saline. This study indicates that mazindol can serve as a reinforcer and that the relationship between total session intake, unit dosage, and self-administration frequency of mazindol are similar to these seen with other reinforcing psychomotor stimulant drugs.
Topics: Animals; Cocaine; Conditioning, Classical; Dose-Response Relationship, Drug; Haplorhini; Indoles; Injections, Intravenous; Macaca mulatta; Male; Mazindol; Reinforcement Schedule
PubMed: 817301
DOI: 10.1016/0091-3057(76)90017-4 -
Toxins Apr 2021Botulinum toxin type A (BoNT-A) injection patterns customized to each patient's unique tremor characteristics produce better efficacy and lower adverse effects compared...
Botulinum toxin type A (BoNT-A) injection patterns customized to each patient's unique tremor characteristics produce better efficacy and lower adverse effects compared to the fixed-muscle-fixed-dose approach for Essential Tremor (ET) and Parkinson's disease (PD) tremor therapy. This article outlined how a kinematic-based dosing method to standardize and customize BoNT-A injections for tremors was developed. Seven ET and eight PD participants with significant tremor reduction and minimal perceived weakness using optimized BoNT-A injections determined by clinical and kinematic guidance were retrospectively selected to develop the kinematic-based dosing method. BoNT-A dosages allocated per joint were paired to baseline tremor amplitudes per joint. The final kinematic-based dosing method was prospectively utilized to validate BoNT-A injection pattern selection without clinical/visual assessments in 31 ET and 47 PD participants with debilitating arm tremors (totaling 122 unique tremor patterns). Whole-arm kinematic tremor analysis was performed at baseline and 6-weeks post-injection. Correlation and linear regression analyses between baseline tremor amplitudes and the change in tremor amplitude 6-weeks post-injection, with BoNT-A dosages per joint, were performed. Injection patterns determined using clinical assessment and interpretation of kinematics produced significant associations between baseline tremor amplitudes and optimized BoNT-A dosages in all joints. The change in elbow tremor was only significantly associated with the elbow total dose as the change in the wrist and shoulder tremor amplitudes were not significantly associated with the wrist and shoulder dosages from the selected 15 ET and PD participants. Using the kinematic-based dosing method, significant associations between baseline tremor amplitudes and the change (6-weeks post-first treatment) in tremor at each joint with BoNT-A dosages for all joints was observed in all 78 ET and PD participants. The kinematic-based dosing method provided consistency in dose selection and subsequent tremor reduction and can be used to standardize tremor assessments for whole-arm tremor treatment planning.
Topics: Acetylcholine Release Inhibitors; Algorithms; Biomechanical Phenomena; Botulinum Toxins, Type A; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Drug Therapy, Computer-Assisted; Essential Tremor; Humans; Injections; Parkinson Disease; Prospective Studies; Retrospective Studies; Time Factors; Treatment Outcome; Upper Extremity
PubMed: 33917695
DOI: 10.3390/toxins13040264 -
Journal of Veterinary Internal Medicine Jan 2020Refractory congestive heart failure (CHF) and associated diuretic resistance are not well defined.
BACKGROUND
Refractory congestive heart failure (CHF) and associated diuretic resistance are not well defined.
OBJECTIVES
To characterize renal function, electrolyte concentrations, indices of diuretic efficacy, and renin-angiotensin-aldosterone system (RAAS) activation in dogs with naturally occurring heart disease (HD) in American College of Veterinary Internal Medicine stages B1, B2, C, and D and to determine their usefulness in defining HD stages.
ANIMALS
Group 1:149 dogs with HD stages B1, B2, C, and D. Group 2:22 dogs with HD stages C and D.
METHODS
Group 1: Renal parameters, serum and urine electrolyte and diuretic concentrations, and urine aldosterone concentrations were measured. Medication dosages and measured variables were compared among stages. Correlation of furosemide dosages to serum concentrations was explored. Group 2: Angiotensin-converting enzyme activity and RAAS components were measured and compared among CHF stages.
RESULTS
Serum chloride concentration was the best differentiator of HD stage. Furosemide PO dosages (≤6 mg/kg/day) were weakly correlated with serum furosemide concentrations, whereas higher dosages were not significantly correlated. Angiotensin-converting enzyme inhibitor dosage and RAAS inhibition were greater in stage D, compared to stage C dogs.
CONCLUSIONS AND CLINICAL IMPORTANCE
Hypochloremia is a useful marker for stage D HD in dogs. Poor furosemide dosage correlation to serum concentration may indicate variable and poor absorption, especially at higher dosages, advanced disease, or both. A small number of stage D dogs met proposed criteria for diuretic resistance. Greater RAAS inhibition in stage D versus stage C indicates effectiveness of RAAS-suppressive treatments in this group of dogs with refractory CHF.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Diuretics; Dog Diseases; Dogs; Electrolytes; Heart Diseases; Kidney Function Tests; Pyridazines; Renin-Angiotensin System; Spironolactone
PubMed: 31769114
DOI: 10.1111/jvim.15662 -
The International Journal of... 2004It is well established that concentration gradients of signaling molecules (the so-called "morphogens") organize and pattern tissues in developing animals. In... (Review)
Review
It is well established that concentration gradients of signaling molecules (the so-called "morphogens") organize and pattern tissues in developing animals. In particular, studies in Drosophila and different vertebrates have shown that gradients of the Wnt, Hedgehog (Hh) and transforming growth factor-beta (TGF-beta) families of morphogens play critical roles in limb patterning. Morphogens are often expressed in organizing centres and can act over a long range to coordinate the patterning of an entire field of cells. These observations imply that exposure to different concentrations of these diffusible factors may trigger differential cellular responses. In order to study these dosage-dependent Wnt/beta-catenin signaling effects, we have generated several hypomorphic mutant alleles at the mouse Apc locus and studied their cellular and phenotypic outcomes in stem cell renewal and differentiation, and in tumorigenesis. The results clearly show that Apc mutations differentially affect the capacity of stem cells to differentiate in a dosage-dependent fashion. Likewise, different Apc mutations (and the corresponding Wnt signaling dosages) confer different degrees of susceptibility to tumorigenesis in the corresponding mouse models. These results have implications for the understanding of the molecular and cellular basis of tumor initiation by defects in the Wnt pathway. We propose a model in which adult somatic stem cell compartments are characterized by tissue-specific beta-catenin threshold levels for cell proliferation, differentiation and apoptosis. Different APC mutations will result in different levels of beta-catenin signaling, thus conferring different degrees of tumor susceptibility in different tissues. Hence, beta-catenin dosage-dependent effects may not only explain how a single pathway is involved in the development and homeostasis of different tissues, but also its pleiotrophic role in tumorigenesis.
Topics: Adenomatous Polyposis Coli Protein; Alleles; Animals; Cell Differentiation; Colorectal Neoplasms; Disease Progression; Dose-Response Relationship, Drug; Genes, APC; Mice; Models, Biological; Models, Genetic; Mutation; Neoplasms; Phenotype; Signal Transduction; Stem Cells; Transforming Growth Factor beta
PubMed: 15349813
DOI: 10.1387/ijdb.041807cg -
Cancer Chemotherapy and Pharmacology Oct 2021High-dose methotrexate (HDMTX) is administered for the treatment of a variety of malignant tumors. Wide intra- and inter-individual variabilities characterize the...
PURPOSE
High-dose methotrexate (HDMTX) is administered for the treatment of a variety of malignant tumors. Wide intra- and inter-individual variabilities characterize the pharmacokinetics of MTX, which is mostly excreted renally. HDMTX dosages are prescribed as a function of body surface area whereas dose adjustments depending on renal function are not well defined. We develop a population pharmacokinetic model with a physiological description of renal excretion as the basis for clinical tools able to suggest model-informed dosages and support therapeutic monitoring.
METHODS
This article presents a minimal physiologically based pharmacokinetic (PBPK) model for HDMTX, which specifically accounts for individual characteristics such as body weight, height, gender, age, hematocrit, and serum creatinine to provide individualized predictions. The model supplies a detailed and mechanistic description of capillary and cellular exchanges between plasma, interstitial fluid, and intracellular fluid compartments, and focuses on an individualized description of renal excretion.
RESULTS
The minimal PBPK model is identified and validated with a literature dataset based on Chinese patients suffering from primary central nervous system lymphoma. A comparison with a pharmacokinetic model from the literature suggests that the proposed model provides improved predictions. Remarkably, the model does not present any significant bias in a wide range of degrees of renal function.
CONCLUSION
Results show that model predictions can capture the wide intra- and inter-individual variability of HDMTX, and highlight the role played by the individual degree of renal function. The proposed model can be the basis for the development of clinical decision-support systems for individualized dosages and therapeutic monitoring.
Topics: Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Kidney; Male; Methotrexate; Models, Biological; Neoplasms
PubMed: 34120234
DOI: 10.1007/s00280-021-04305-2 -
Methods and Protocols Nov 2023This research evaluates extracts from the bark of and as coagulating agents for removing turbidity in domestic wastewater, considering the coagulant dosage and pH of...
This research evaluates extracts from the bark of and as coagulating agents for removing turbidity in domestic wastewater, considering the coagulant dosage and pH of the wastewater. ANOVA was conducted to assess differences between the coagulants, dosages, and pH, with three pH levels (5, 8, and 9) and six dosages (7, 9, 11, 13, 15, and 17 mL per 1000 mL of wastewater) at a significance level of α = 0.05, and both the -value and effect size were evaluated. This study found that the mucilaginous compound from the bark of performed better in reducing turbidity levels, with an average reduction of 30.2 NTU (Nephelometric Turbidity Unit) ( [25.9 NTU; 34.5 NTU], α = 0.05) at a pH of 5, and an average initial NTU of 102.2. This represents an average reduction of 70.45%. The dosage factor did not show significant effects on turbidity reduction, which opens the possibility for further study to determine the optimal dosage of the best coagulant.
PubMed: 37987352
DOI: 10.3390/mps6060105 -
Acta Naturae Oct 2010Sex chromosome evolution is accompanied by significant divergence in morphology and gene content and results in most genes of one of the sex chromosomes being present in...
Sex chromosome evolution is accompanied by significant divergence in morphology and gene content and results in most genes of one of the sex chromosomes being present in two dosages in one sex and in one dosage in the other. To eliminate the difference in the expression levels of these genes between sexes and to restore equal expression levels of the genes between sex chromosomes and autosomes, mechanisms of dosage compensation have appeared. Studies of three classical objects,Drosophila melanogaster,Caenorhabditis elegans, and mammals, have shown that dosage compensation of X-linked genes can be achieved through completely different chromosome-wide mechanisms. New data on sex chromosome gene expression demonstrating that many sex chromosome genes can be expressed at different levels in males and females were recently obtained from birds and butterflies. In this review, dosage compensation mechanisms inD. melanogaster,C. elegans, and mammals are considered and the data on sex chromosome gene expression in birds and butterflies, and their influence on our view of dosage compensation, are discussed.
PubMed: 22649662
DOI: No ID Found