Dual action of morphine and related drugs on compulsive gnawing of rats

1976 ◽  
Vol 46 (1) ◽  
pp. 87-91 ◽  
Author(s):  
Felix Bergmann ◽  
Moshe Chaimovitz ◽  
Varda Pasternak
Keyword(s):  
Dual Action ◽  
Compulsive Gnawing

Two Firms Shelve Dual-Action Diabetes Drugs

2006 ◽  
Vol 4 (7) ◽  
pp. 4
Author(s):  
MIRIAM E. TUCKER
Keyword(s):  
Dual Action

The Action of an Aniline Derivative (AN 162) on Blood Coagulation and on Platelets

1971 ◽  
Vol 26 (01) ◽  
pp. 145-166
Author(s):  
E Deutsch ◽  
K Lechner ◽  
K Moser ◽  
L Stockinger
Keyword(s):  
Blood Coagulation ◽  
Citric Acid Cycle ◽  
Second Phase ◽  
Aniline Derivative ◽  
Acid Cycle ◽  
Enhancing Effect ◽  
Low Concentrations ◽  
Dual Action ◽  
High Concentrations ◽  
Induced Aggregation

Summary1. The aniline derivative AN 162, Donau Pharmazie, Linz, Austria, has a dual action on the blood coagulation: an anticoagulant and an coagulation enhancing effect.2. The anticoagulant action may only be demonstrated with high concentrations (over 1 X 10”3 M related to plasma) preferentially in PPP. It is partially caused by an inhibition of the endogenous way of generation of the prothrombin converting principle. In addition it is suggested that it interferes with the fibrinogen-fibrin reaction in a manner not yet understood.3. The coagulant action is caused by a greater availability of platelet constituents at low concentrations of AN 162 (over 1 × 10-4 M) and by the induction of a release reaction at higher concentrations. The platelet factors 3 and 4, serotonin, adenine, and acid phosphatase are released.4. AN 162 inhibits platelet aggregation. This inhibition can be demonstrated by the PAT of Breddin and in the stirred aggregation test of Born. It is more effective to inhibit the collagen-induced and the second phase of the adrenaline-induced aggregation than the ADP induced one. The platelet retention (test of Hellem) is also reduced.5. The action of AN 162 on the platelets is caused by a damage of the platelet membrane which becomes permeabel for both, soluble platelet constitutents and granula.6. AN 162 interferes with the energy metabolism of the platelets. It causes a loss of ATP, and inhibits the key-enzymes of glycolysis, citric acid cycle, fatty acid oxydation and glutathione reduction.7. AN 162 inhibits the growth of fibroblasts without influence on mitosis.

Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Triple Negative ◽  
Growth Factor Receptor ◽  
Engineered Nanoparticles ◽  
Efficacy Evaluation ◽  
Dual Action ◽  
Epidermal Growth ◽  
Laminin 411 ◽  
Immunologic Analysis

Engineered nanoparticles are widely used for delivery of drugs but frequently lack proof of safetyfor cancer patient's treatment. All-in-one covalent nanodrugs of the third generation have beensynthesized based on a poly(β-L-malic acid) (PMLA) platform, targeting human triple-negativebreast cancer (TNBC). They significantly inhibited tumor growth in nude mice by blockingsynthesis of epidermal growth factor receptor, and α4 and β1 chains of laminin-411, the tumorvascular wall protein and angiogenesis marker. PMLA and nanodrug biocompatibility and toxicityat low and high dosages were evaluated in vitro and in vivo. The dual-action nanodrug and singleactionprecursor nanoconjugates were assessed under in vitro conditions and in vivo with multipletreatment regimens (6 and 12 treatments). The monitoring of TNBC treatment in vivo withdifferent drugs included blood hematologic and immunologic analysis after multiple intravenousadministrations. The present study demonstrates that the dual-action nanoconju-gate is highlyeffective in preclinical TNBC treatment without side effects, supported by hematologic andimmunologic assays data. PMLA-based nanodrugs of the Polycefin™ family passed multipletoxicity and efficacy tests in vitro and in vivo on preclinical level and may prove to be optimizedand efficacious for the treatment of cancer patients in the future.

scholarly journals Molecular Insights into an Antibiotic Enhancer Action of New Morpholine-Containing 5-Arylideneimidazolones in the Fight against MDR Bacteria

2021 ◽  
Vol 22 (4) ◽  
pp. 2062
Author(s):  
Aneta Kaczor ◽  
Karolina Witek ◽  
Sabina Podlewska ◽  
Veronique Sinou ◽  
Joanna Czekajewska ◽  
...  
Keyword(s):  
Molecular Modelling ◽  
Efflux Pump ◽  
Gram Negative Bacteria ◽  
Potential Mechanism ◽  
Multidrug Efflux ◽  
Aromatic Rings ◽  
Allosteric Site ◽  
Multidrug Efflux Pump ◽  
Dual Action

In the search for an effective strategy to overcome antimicrobial resistance, a series of new morpholine-containing 5-arylideneimidazolones differing within either the amine moiety or at position five of imidazolones was explored as potential antibiotic adjuvants against Gram-positive and Gram-negative bacteria. Compounds (7–23) were tested for oxacillin adjuvant properties in the Methicillin-susceptible S. aureus (MSSA) strain ATCC 25923 and Methicillin-resistant S. aureus MRSA 19449. Compounds 14–16 were tested additionally in combination with various antibiotics. Molecular modelling was performed to assess potential mechanism of action. Microdilution and real-time efflux (RTE) assays were carried out in strains of K. aerogenes to determine the potential of compounds 7–23 to block the multidrug efflux pump AcrAB-TolC. Drug-like properties were determined experimentally. Two compounds (10, 15) containing non-condensed aromatic rings, significantly reduced oxacillin MICs in MRSA 19449, while 15 additionally enhanced the effectiveness of ampicillin. Results of molecular modelling confirmed the interaction with the allosteric site of PBP2a as a probable MDR-reversing mechanism. In RTE, the compounds inhibited AcrAB-TolC even to 90% (19). The 4-phenylbenzylidene derivative (15) demonstrated significant MDR-reversal “dual action” for β-lactam antibiotics in MRSA and inhibited AcrAB-TolC in K. aerogenes. 15 displayed also satisfied solubility and safety towards CYP3A4 in vitro.

scholarly journals Local Anesthetic Delivered with a Dual Action Ring and Injection Applicator Reduces the Acute Pain Response of Lambs during Tail Docking

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2242
Author(s):  
Alison Small ◽  
Danila Marini ◽  
Ian Colditz
Keyword(s):  
Acute Pain ◽  
Local Anesthetic ◽  
Dual Function ◽  
Treatment Groups ◽  
Ewe Lambs ◽  
Tail Docking ◽  
Function Ring ◽  
Dual Action ◽  
Abnormal Behaviors ◽  
Control Sham

Docking the tail of lambs is a standard husbandry procedure and is achieved through several techniques including clamps, hot or cold knives and latex rings, the last of which is the most popular. All tail docking methods cause acute pain which can be reduced by application of local anesthetic, however precise anatomical injection for optimal efficacy requires considerable skill. This pen trial evaluated the ability of local anesthetic (LA) delivered with a dual function ring applicator/injector to alleviate acute tail docking pain. Thirty ewe lambs were assigned to one of three treatment groups (n = 10 per group): ring plus local anesthetic (Ring LA), ring only (Ring) and sham handled control (Sham). Lambs were videoed and their behavior categorized every five minutes for the first hour and every 10 min for the subsequent two hours after treatment. There was a significant effect (p < 0.001) of treatment on total active pain related behaviors in the first hour, with Ring lambs showing higher counts compared to Ring LA or Sham. Ring lambs also displayed a significantly higher count of combined abnormal postures (p < 0.001) than Ring LA or Sham lambs. Delivery of 1.5 mL of 2% lignocaine via the dual action device abolished abnormal behaviors and signs of pain in Ring LA lambs. However, lambs in the Ring LA group spent less time attempting to suckle compared to Ring and Sham lambs, suggesting that some residual discomfort remained.

scholarly journals Dual Action of Sulfated Hyaluronan on Angiogenic Processes in Relation to Vascular Endothelial Growth Factor-A

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Linda Koehler ◽  
Gloria Ruiz-Gómez ◽  
Kanagasabai Balamurugan ◽  
Sandra Rother ◽  
Joanna Freyse ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Computational Study ◽  
Treatment Strategies ◽  
Vascular Endothelial ◽  
Heparin Binding ◽  
Heparin Binding Domain ◽  
Dual Action ◽  
Prospective Application ◽  
Endothelial Growth Factor

AbstractPathological healing characterized by abnormal angiogenesis presents a serious burden to patients’ quality of life requiring innovative treatment strategies. Glycosaminoglycans (GAG) are important regulators of angiogenic processes. This experimental and computational study revealed how sulfated GAG derivatives (sGAG) influence the interplay of vascular endothelial growth factor (VEGF)165 and its heparin-binding domain (HBD) with the signaling receptor VEGFR-2 up to atomic detail. There was profound evidence for a HBD-GAG-HBD stacking configuration. Here, the sGAG act as a “molecular glue” leading to recognition modes in which sGAG interact with two VEGF165-HBDs. A 3D angiogenesis model demonstrated the dual regulatory role of high-sulfated derivatives on the biological activity of endothelial cells. While GAG alone promote sprouting, they downregulate VEGF165-mediated signaling and, thereby, elicit VEGF165-independent and -dependent effects. These findings provide novel insights into the modulatory potential of sGAG derivatives on angiogenic processes and point towards their prospective application in treating abnormal angiogenesis.

scholarly journals COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection

2021 ◽  
Vol 14 (1) ◽  
pp. 71
Author(s):  
Katarzyna Kotfis ◽  
Kacper Lechowicz ◽  
Sylwester Drożdżal ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Tomasz K. Wojdacz ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Potential ◽  
Severe Pneumonia ◽  
Therapeutic Benefit ◽  
World Health ◽  
Therapeutic Effects ◽  
Severe Acute Respiratory Infection ◽  
Dual Action ◽  
Health Organization ◽  
Transmembrane Serine Protease

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin–angiotensin–aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.

scholarly journals Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

2021 ◽  
Vol 22 (9) ◽  
pp. 4717
Author(s):  
Jin-Young Lee ◽  
Da-Ae Kim ◽  
Eun-Young Kim ◽  
Eun-Ju Chang ◽  
So-Jeong Park ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Map Kinases ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Dual Action ◽  
Dose Dependent ◽  
Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

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