Search results for "imidazoles"
showing 10 items of 272 documents
Bronchodilator and anti-inflammatory activities of SCA40: studies in human isolated bronchus, human eosinophils, and in the guinea-pig in vivo.
1998
There is currently interest in the use of inhibitors of cyclic nucleotide phosphodiesterases (PDE) as potential anti-asthma agents. In this study we examined the effects of SCA40 (6-bromo-8-methylaminoimidazol-[1,2-a] pyrazine-2-carbonitrile), a preferential inhibitor of PDE 3 also endowed with PDE 4 and 5 inhibitory activities, on isolated bronchus and eosinophil functions and in an animal model of asthma. SCA40 (1 nM-0.1 mM) produced concentration-dependent inhibition of spontaneous and stimulated tone of human isolated bronchus and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 against spontaneous tone (6.52 +/- 0.10) was grea…
Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.
2015
A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Rena…
Pantoprazole: from drug metabolism to clinical relevance.
2008
Conditions requiring inhibition of acid secretion, such as gastro-oesophageal reflux disease (GORD), peptic ulcers, non-ulcer dyspepsia or the use of NSAIDs, are very common, and their prevalence is expecting to rise as they are seen predominantly amongst the elderly. Among the drugs available to inhibit acid secretion, proton pump inhibitors (PPI) have been shown to have the best efficacy-safety ratio and have been used widely.This paper was intended to provide an overall presentation of one of these PPIs, pantoprazole.This study was first intended to give an overview of pantoprazole, so a Medline search was conducted using pantoprazole as unique search term, without publication date restr…
Effect of histamine on the longitudinal and circular muscle of the oestrogen dominated rat uterus.
1993
The response of the longitudinal and circular myometrial strips to histamine was studied in oestrogen-treated rats. Histamine produced a dose-related inhibitory response in KCl-contracted longitudinal and circular uterine strips. Histamine was equipotent in producing the relaxant response but the maximal effect achieved in the longitudinal muscle was higher than the circular one. Ranitidine antagonized the histamine-induced relaxation with a similar dose ratio in both longitudinal and circular strips. Clemizole and reserpine treatment did not produce any modification of the dose-response curve to histamine. In the longitudinal and circular strips which were not preconstricted by KCl, neithe…
Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retr…
2021
Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Ita…
Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner – A quantitative in vitro gene expression analy…
2010
Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ). There are two groups of bisphosphonates: the nitrogen-containing bisphosphonates, e.g. zoledronate and ibandronate, and the non-nitrogen-containing bisphosphonates, e.g. clodronate. Their impact on bone metabolism seems to differ. The objective of this study was to compare the osteogenic differentiation potency of these two pharmacologic groups. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5×10(-5) M, 5×10(-6) M and 5×10(-7) M over the experimental …
Managing Bleeding Complications in Patients Treated with the Old and the New Anticoagulants
2010
An increasing number of patients receive anticoagulant therapy to prevent and treat arterial or venous thromboembolism. The major complication of anticoagulant therapy is the increase of the individual bleeding risk. All anticoagulant drugs can cause haemorrhages, that can sometimes be life-threatening. Although heparins and the vitamin K antagonists have been the most widely used anticoagulants for decades, the correct management of bleeding complications associated with these agents has been poorly studied. More recently, new anticoagulant drugs, both parenteral and oral, have been approved for clinical use. Currently, none of these new agents has a specific antidote, and little advise ca…
Gastrointestinal disorders and dabigatran.
2012
Anticoagulants play an important role in the prevention and treatment of a variety of acute and chronic thromboembolic disorders such as primary prevention and treatment of venous thromboembolism or prevention of stroke and systemic embolism in atrial fibrillation just to name of few. Within recent years, a promising new oral anticoagulant, the direct thrombin inhibitor dabigatran etexilate (dabigatran) successfully underwent clinical development and has emerged as an alternative to vitamin K antagonists according to a variety of recently revised and updated international guidelines referring to the indication of stroke prevention in atrial fibrillation. Considering the intensive clinical u…
Dexrazoxane shows cytoprotective effects in zoledronic acid-treated human cells in vitro and in the rabbit tibia model in vivo
2012
Abstract Introduction Bisphosphonates are important and effective drugs in oncology and osteoporosis therapy. They accumulate in the bone matrix becoming released and active by bone resorption. This leads to effective inhibition of tumor cells and bone degradation. A side effect of bisphosphonates similar to other drugs like denosumab is osteonecrosis of the jaws (ONJ). This problem mostly occurs after tooth extraction. We studied the cytoprotectant dexrazoxane known from anthracycline chemotherapy for cytoprotection in nitrogen-containing bisphosphonate treated cells and in the rabbit tibia model to evaluate a possible value in ONJ management. Materials & methods Human osteoblasts (HOB) P2…
Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors
2023
The present work describes the design and development of seventeen pyrimidine-clubbed benzimidazole derivatives as potential dihydrofolate reductase (DHFR) inhibitors. These compounds were filtered by using ADMET, drug-likeness characteristics calculations, and molecular docking experiments. Compounds 27, 29, 30, 33, 37, 38, and 41 were chosen for the synthesis based on the results of the in silico screening. Each of the synthesized compounds was tested for its in vitro antibacterial and antifungal activities using a variety of strains. All the compounds showed antibacterial properties against Gram-positive bacteria (Staphylococcus aureus and Staphylococcus pyogenes) as well as Gram-negativ…