@article{ author = {Pousti, Abbas and Malihi, Golrokh and Bakhtiarian, Azam and Abdollahi, Zahr}, title = {The Comparative Effects of Four Antihistamines on Isolated Rat Atria}, abstract ={It has been reported that some of H1 receptor antagonists have important effects on cardiovascular system. Terfenadine as a non-sedative H1 receptor antagonist has an arrhythmogenic activity. In this study we have shown the effects of four antihistamine drugs: terfenadine, loratadine, clemastine and diphenhydramine, on the rate and contractions of isolated rat atria. Terfenadine (1-10 µM) caused a negative chronotropic effect (19.5-80%) and arrhythmia after 10 min. followed by a decrease in the contractile force by (7.5%), and finally after 45 min. asystolia occurred. Loratadine (30-150 µM) decreased the rate of contractions (10-82%) after 10 min. the contractile force of atria was decreased (10-19%) after 20 min. Loratadine did not produce any arrhythmia. Diphenhydramine (5-20 µM) produced bradycardia (14.5-43%) after 20 min and decreased the contractile force (2.5-40%) after 40 min. Clemastine (3-10 µM) produced negative chronotropic and inotropic effect by (11.5-42%) and (10-58%) respectively. These findings indicate that all four drugs caused bradycardia and reduced contractile force, but in the case of terfenadine, it also had arrhythmogenic activity. Loratadine had the least cardiotoxic effect.}, Keywords = {}, volume = {1}, Number = {2}, pages = {20-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-17-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-17-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Tabeie, Faraj and Bolouri, Bahram and Jalilian, Amir Reza and Mossaffa, Nariman and Rajabi, Hosein and NeshandarAsli, Eisa and Labibi, Farzaneh and Karimian, Ali Reza and Shirazi, Behrooz}, title = {Dynamic Distribution of 67Ga-Bleomycin Complex and Carrier Free 67Gallium in Normal Mice}, abstract ={This study reports the labeling of Gallium-Bleomycin (67Ga-BLM) complex as a radiopharmaceutical and optimization of its labeling conditions; pH, reaction time, temperature, concentration of bleomycin and its biodistribution in normal Bulb C mice. The biodistribution of the complex was compared with 67Ga-Cl3 in 11 selected organs including blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content, and bladder at five selected times of 1, 2, 4, 24 and 48 hours after injection. Cyclotron produced 67Gallium was labeled with bleomycin under Thakur method. The optimized pH condition was found 2 at temperature of 90ºC for reaction temperature of 30 minutes when 0.5 mg of bleomycin was mixed with 1 mCi of 67Ga-Cl3. Pharmacokinetic data indicated higher uptakes of 67Ga-BLM in all 11 tissues except blood, liver and spleen in comparison with 67Ga-Cl3. The average of total uptakes from 67Ga-BLM and 67Ga-Cl3 radiopharmaceuticals at one hour after injection were 73.35% and 53.55% then reduced to 14.55% and 25.2% after 48 hours respectively. The blood uptake of 67Ga-Cl3 was higher than 67Ga-BLM in all time intervals. Bladder uptake of 67Ga-BLM was highest among 11 tissues at all time intervals but the uptake of 67Ga-Cl3 was only highest at first hour after the injection. The results indicated the high stability of the complex both in-vitro and in-vivo, and yet excreted faster than carrier free 67Gallium. The effective half life of 67Ga-BLM complex was found 48.15 hours.}, Keywords = {}, volume = {1}, Number = {2}, pages = {24-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-16-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-16-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Turner, A.J.}, title = {NEP, ACE and Homologues: The Pathophysiology of Membrane Metalloproteases}, abstract ={The zinc metalloprotease, neprilysin (NEP), plays a role in the metabolism of cardiovascular, inflammatory and neuropeptides, including mitogenic peptides such as bombesin. In the cardiovascular system, NEP has a primary role in the inactivation of natriuretic peptides but also contributes to local metabolism of angiotensin, endothelins and bradykinin. Hence NEP is seen as a potential therapeutic target and drug development is facilitated by its recent structural solution. In prostate cancer, NEP is dramatically down-regulated allowing mitogenic peptides to drive androgen-independent progression of the disease. NEP also contributes to the catabolism of the neurotoxic beta-amyloid peptide in Alzheimer’s disease. Thus up- or downregulation of NEP activity critically affects peptide metabolism and can contribute to the pathophysiology of a number of diseases. The human genome contains seven NEP-like enzymes, including the endothelin converting enzymes (ECE) and aspects of their physiology and properties will be highlighted. We have also identified a novel human homologue of the zinc metalloprotease, angiotensin converting enzyme (ACE). This enzyme (ACEH) hydrolyses angiotensins I and II but not bradykinin and functions exclusively as a carboxypeptidase. Its localization and possible roles in regulation of the renin-angiotensin and other peptide systems will be described and compared with those of ACE itself.}, Keywords = {}, volume = {1}, Number = {2}, pages = {30-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-15-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-15-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Meyer, Edgar and Khademi, Shahram and Botos, I. and Meyer, E.F.}, title = {Structural Overview Of Mammalian Zinc Metalloproteinases}, abstract ={Matrix metalloproteinases (MMP) are crucial for homeostasis (tissue remodelling and repair, bone growth, wound healing, etc.) and pathology (metastasis, angiogenesis, aneurysm rupture, etc.). Upregulated MMPs from macrophages are thus a two-edged sword, playing both defensive and aggressive roles. The related family of ADAMs (a disintegrin and a metalloproteinase) is sometimes overlooked because of classification peculiarities. The best-studied ADAM-17, tumor necrosis factor a convertase (TNF-a), is a membrane-bound “shedase” that releases a membrane-bound cytokine, tumor necrosis factor a (TACE). Many of the ADAMs have remarkable structural and mechanistic and inhibitor proclivities similar to the MMPs; the potential for inhibitor side reactions and drug toxicities abounds. Over the past 10 years the crystallographic study of proMMPs, MMPs, and ADAMs in free and complexed forms has revealed the mechanistic and structural nature of these macromolecules to atomic resolution. These results will be reviewed and indications for future work will be presented. Special attention will be given to visualization tools to assist with the conceptualization of complex molecular interactions. (Support provided by the Robert A. Welch Foundation, the US National Science Foundation, and the R.W. Johnson Pharmaceutical Research Institute).}, Keywords = {}, volume = {1}, Number = {2}, pages = {31-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-14-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-14-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Mahmoudian, Massou}, title = {Computer Aided Molecular Modeling Of Membrane Metalloprotease}, abstract ={Molecular modeling is a set of computational techniques for construction of 3D structure of a protein especially membrane bound proteins whose structures can not be elucidated using experimental techniques. These techniques has been applied in the study of membrane metalloproteases for comparing wild and mutated enzymes, docking inhibitors in the catalytic site and examination of binding pocket and mode of inhibitors binding. The present study was carried out to construct 3D structure of strmelysin-3, an important member of this family, using computer aided techniques to shed light on its biological function and provide a 3 dimensional model which could facilitate the rational design of inhibitors. The results of homology search using FASTA between the sequence of human stromelysine-3 and protein data bank showed that 1fbl has the highest similarity and this protein was used to construct the 3D structure of human stromelysin-3. The results of this modeling study showed that this enzyme has a folding structure similar to haemopexin, i.e. existence of a four-bladed structure like the flights of a dart. Zn binding and catalytic activity were described. Similar to other Zn metalloproteases His-215, His-219 and Glu-216 form the coordinates of Zn atom. It is found that the modeled human stromelysine is thermodynamically stable and agrees with biochemical data.}, Keywords = {}, volume = {1}, Number = {2}, pages = {32-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-13-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-13-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Guedez, L. and Stetler-Stevenson, W.G.}, title = {Changing Roles of Matrix Metalloproteases and Their Inhibitors, TIMPs, During Tumor Progression and Angiogenesis}, abstract ={Inhibition of matrix-metalloproteinases (MMPs) by tissue inhibitors of metalloproteinases (TIMPs) has been shown in vivo to decrease metastasis and tumor-associated angiogenesis. Our laboratory is interested in understanding the role of these proteins at the pericellular microenvironment of tumor and endothelial cells. Secretion of MMPs by tumor cells enables the migration, invasion and metastasis of malignant cells. However, these proteases have been shown to regulate cell behavior by novel mechanisms proximal to the cell membrane. Novel roles of MMPs include cleavage and processing of growth and angiogenic factors and their receptors. In addition, TIMPs can inhibit these novel MMP functions. However, TIMPs can also interact and bind to cell membrane proteins, modifying signal transduction pathways independently from their MMP inhibitory action. In order to study the role of MMPs/TIMPs in the pericellular environment during angiogenesis, we have developed and in vivo angiogenesis assay. A semi-enclosed sili one implant containing a constant volume of reconstituted extracellular matrix is pre-mixed with angiogenic factors and implanted subcutaneously in mice. Our preliminary results demonstrate that the angiogenic response can be monitored and objectively quantitated after 9 days. We are currently using this novel assay to study the role of various MMPs in angiogenesis by using MMP-/TIMP transgenic/knock-out mice.}, Keywords = {}, volume = {1}, Number = {2}, pages = {33-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-11-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-11-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Lehoux, Stephanie and Tronc, François and Tedgui, Alai}, title = {Metalloproteinases, Mechanical Factors and Vascular Remodeling}, abstract ={Chronic increases in arterial blood flow elicit an adaptive response of the arterial wall, leading to vessel enlargement and reduction in wall shear stress to physiological baseline value. Release of nitric oxide from endothelial cells exposed to excessive shear is a fundamental step in the remodeling process, and potentially triggers a cascade of events, including growth factor induction and matrix metalloproteinase activation, that together contribute to restructuralization of the vessel wall. NO synthesis blockade in vivo inhibits adaptive wall shear stress regulation in vessels subjected to chronic increased blood flow. This effect is partial, indicative that other factors are probably involved. The pathways by which the remodeling action of NO is mediated include metalloproteinase activation and possibly implicate the induction of growth factor mitogenic activity as well. Furthermore, matrix metalloproteinase (MMP) activation is required for adaptive arterial remodeling (IEL fragmentation and arterial enlargement) to occur. These observations are significant since adaptive vascular enlargement and remodeling are known to accompany early human coronary atherosclerosis, and exaggerated expression of MMPs, in particular MMP-2, is now known to be a ubiquitous marker of aortic aneurysms, and could reflect abnormal flow-induced vessel remodeling. Hence understanding the process of vascular remodeling could help explain how changes in blood vessel wall structure occur in the context of atherosclerosis or aortic aneurisms.}, Keywords = {}, volume = {1}, Number = {2}, pages = {34-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-12-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-12-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Huovila, Ari-Pekka J.}, title = {ADAM Gene Expression in The Adult CNS and Genetic Aberrations in Cancer Cells}, abstract ={ADAM metalloprotease-disintegrins share a common modular structure of functional domains for proteolytic, cell adhesion, and signaling interactions. The metalloprotease domain of oughly half of the known ADAMs contain an intact consensus metzincin catalytic site, and they are thus thought to function as active metalloproteases. The types of interactions mediated by ADAMs are expressly conspicuous in the CNS. However, the information of ADAM functions in the adult CNS remains fragmentary while the neural ADAM research has mainly been focused at the neural development. Nevertheless, ADAMs are emerging as a major CNS metalloprotease family, implicated in, e. g., alpha-secretase processing of amyloid precursor protein (APP), proteolytic activation of cytokines and growth factors, and ectodomain shedding of cell surface receptors. An important prerequisite for exploration of individual ADAMs is detailed knowledge of their expression in the CNS. Here, an update on CNS ADAM gene expression will be presented, including a novel potentionally proteolytic ADAM. Their dual potential to mediate both proteolysis and cell-cell contacts raises also the question about the involvement of ADAMs in the pathobiology of malignancy. Indeed, ADAMs have been associated with several types of cancer. Here, novel data on genomic rearrangements and aberrant pre-mRNA splicing of ADAM15 will be presented, suggesting that one of the impairments in the genetic machinery in cancer cells may be at the level of post-transcriptional processing.}, Keywords = {}, volume = {1}, Number = {2}, pages = {35-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-10-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-10-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Efremov, A.V. and Antonov, A.R.}, title = {The Pathophysiological Aspects of Lymphology of Critical Conditions}, abstract ={In work on Wistar rats with experimental crush syndrome and acute alcohol intoxication shown that alterations of «metabolic profile» are stipulated by the lymphatic system, which emerges as an active component to urgent adaptation in critical situations. It is shown by the expressed infringements of an exchange of electrolytes in plasma. lymph and myocardium at the rats, that can make a part of a pathogenesis of traumatic damage of heart and others organs and reason of mortality in the acute period crush-syndrome and more serious current of the reduction period. On the example of hormones, endorphins, protein, electrolytes and trace elements exchange is shown integral reaction the lymphatic system, directed on the compensation of syndrome «endogenous starving». For the first time suggested a concept of «lymphatic resetting» as system reactions on the extreme influence and is described phenomenon an «lymphoattraction» - selective accumulation of certain metabolites by components the lymphatic system. For the first time suggested a theory of lymphatic system as functional stress-limited system. We found the syndrome of adaptive overload at the traumatic stress. Shown that crush syndrome end acute alcohol intoxication accompanied the «secondary trace elements disturbances». Drawn a conclusion about universality of described reactions for medicine critical conditions.}, Keywords = {}, volume = {1}, Number = {2}, pages = {36-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-9-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-9-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Grigoriev, E.V. and Churlyaev, Yu.A. and Lykova, O.F. and Zorin, N.A. and Denisov, E.N.}, title = {Lactoferrin as a Marker of Systemic Inflammatory Response}, abstract ={Materials and methods. 51 patients, who were ill with generalized peritonitis, went through a prospective randomized research. They were randomized on groups depending on the objective score SAPS (1984): 29 survived people (53%) and 22 people with favorable end (47%). Intensive care and surgical tactics standardized patients. Lactoferrin (LF) as modulator of systemic inflammatory response (SIR) was assessed by immunoferment analysis. Statistical processing was done McNemar test. Results and discussion. In initial condition dynamics of this laboratory marker defined a group with favorable end as patients with granulocytes activation [1]. On the first 24 hours level of LF was marked twice above values of second group (95% confidence interval (CI) 1670-2024 ng/ml; p less than 0.05). Then content of LF was increased for certain in highest limit of rate (95% CI 1104-1310; pless than0.001). LF level in group with nonfavourable end was remained in lowered figures. It was differ with such in group of comparison for certain (95% CI 811-921 ng/ml; pless than0.05). This situation can be explained as repression of nonspecific resistance on repeated effects of endotoxins. Positive connection of LF indices with facts of SIR (r=0.457; pless than0.05) can serve as proof of granulocyte’s activation in group with favorable end [2].}, Keywords = {}, volume = {1}, Number = {2}, pages = {37-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-8-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-8-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Suzic-Todorovic, B. and Djordjevic, D. and Lekic, D. and Strugarevic, E. and Nikolic, B.}, title = {High Frequency Magnetic Fields in Treatment of Osgood-Schlatter Disease}, abstract ={We are studied efficacy of high frequency magnetic fields (HFMFs) in treatment of Osgood-Schlatter disease (OSD) including X-rays signs. THELF system apparatus has been used for treatments on 32 young sportsmen (9-15 years). 18 boys and 14 girls, with HFMFs (base frequency 27.125 MHz, with different impulse repetition frequency of 640 Hz and 320 Hz, and absorbed power 3-5 VA). Injured sportsmen were players with large numbers of high or long jumping such as in the basketball, volleyball, fieldball and rhythmical gymnastics. Time of every daily treatment was 30 mm (640 Hz) and 30 mm (320 Hz) during 28 days but the number of treatment on an average was 28±2. Using The McGill Pain Questionnaire indicated that in mostly cases subjective complaints has been disappeared in a month from of beginning of treatments, which give sportsmen’s opportunity to begin to exercise. In two months they were strongly and in better shape to exercise for a final match. In all cases are confirmed with positive X-rays signs. These results suggest that HFMFs is may be very important method of treatment Osgood-Schlatter disease. Using HFMFs in treatment of Osgood-Schlatter disease we made excellent progress in more rapidly recovering of injured young sportsmen’s.}, Keywords = {}, volume = {1}, Number = {2}, pages = {38-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-7-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-7-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} } @article{ author = {Ziai, Seyed Ali and Salehian, Pirooz and Mahmoudian, Massou}, title = {Study of Serum and Tissues Angiotensin Converting Enzyme (ACE) Activity in Rat with Gentamicin Induced Renal Toxicity}, abstract ={The angiotensin I-converting enzyme (ACE) converts the inactive angiotensin I molecule to the active angiotensin II. ACE is rich in epithelium, endothelium, and neuroepithelial cells and it found largely on the brush border of intestine and kidney proximal tubules. ACE also presents in the serum. Some pulmonary and renal toxic drugs change the serum and tissue ACE contents. In this research ACE activity was studied in rats with gentamicin induced renal toxicity. Rats were sacrificed 1, 3, 5 and 7 days after gentamicin injection. ACE activity was measured in serum, kidney and lung. These data were compared with normal saline-treated rats. Treatment of rats with gentamicin results in renal damage evidenced by proteinuria, polyuria, and decreased creatinine clearance. The damage to the kidney proximal tubule was evident by (a) the histological analysis at light microscopy and (b) the augmentation in the urinary excretion of N-acetyl-?-D-glucosaminidase (NAG). Kidney ACE activity decreased and lung and serum ACE activity didn’t change until day 7. Then lung ACE activity increased significantly at day 7 and kidney and serum ACE activity increased, too. Blood pressure increased significantly on the day 7 that corresponded with the lung ACE activity increment. These data suggest that kidney ACE activity decrease are due to renal damage and an universal signal increases the ACE contents in the body probably to increase systemic blood pressure and subsequently increase glomerular filtration rate (GFR).}, Keywords = {}, volume = {1}, Number = {2}, pages = {39-0}, publisher = {4}, title_fa = {}, abstract_fa ={}, keywords_fa = {}, url = {http://ijpt.iums.ac.ir/article-1-6-en.html}, eprint = {http://ijpt.iums.ac.ir/article-1-6-en.pdf}, journal = {Iranian Journal of Pharmacology and Therapeutics}, issn = {9}, eissn = {10}, year = {2002} }