39 2228-7043 Iran University of Medical Sciences 1818 Physiology FETAL HEART ASSESSMENT BY MAGNETOCARDIOGRAPHY: A PILOT STUDY Asgari A. Weir AI. Quinn A. Shahani U. 1 9 1996 3 1 177 177 13 11 2011 Fetal magnetocardiograph (fMCG) provides a new non-invasive technique for monitoring fetal cardiac wellbeing during the last 10 weeks ofpregnancy. Using a single channel second order SQUID gradiometer located over the maternal abdomen we have successfully recorded QRS complexes in 9 of 11 subjects from 30-40 weeks gestation and full PQRSTcomplexes in all 4 subjects in whom off-line averaging techniques were applied.
1839 Biochemistry RECENT ADVANCES IN TREATMENT OF OP PESTICIDE POISONING Balali M. 1 9 1996 3 1 178 178 26 11 2011 Organophosphate (OP) compounds have largely been used as pesticides and also as nerve agents in Chemical Wars. OP pesticides have frequently been imported and freely available to the public without usage control. Therefore, OP poisoning, mainly intentional type, is very common and accounts for 21.8% (250 patients) of the total admission to the hospital between 21 March 1994 and 20 March 1995. OP compounds induce accumulation of acetyl choline by inhibition of acetyl cholinestrase leading to the stimulation of muscarinic and nicotinic receptors. Muscarinic effects are counteracted successfully by atropine sulfate, but the therapeutic effects of oximes on nicotinic receptors and cholinestrase reactivation have not been observed in clinical practice. Clinical obervations of the author and a report from Sri Lanka (Lancet 339,1992), indicates no therapeutic effects of oximes in OP poisoning. Case notes of 317 Treatment Centres between 21 March 1993 and 20 March 1995 were studied. There were significant positive correlations between the oxime doses and either hospitalization days (r=0.625, p<0.001) or mortality rate (= 0.718, p<0.01). It seems that oximes had no therapeutic effects on OP pesticide poisoning. However, a prospective investigation is currently undertaken to confirm this hypothesis. 1841 Biochemistry RELATIVE BIOAVAILABILITY OF CEPHALEXIN DIFFERENT BRANDS OF CAPSULES Hassanzadeh M. Fazli-Bazzaz S. Shirazie A. 1 9 1996 3 1 179 179 27 11 2011 In a cross over study eight normal human volunteers were employed. The bioavailability of different commercial brands of cephalexin capsules were examined. The relative bioavailability offour brand (J.I,J.II,L.I,L.II) manufactured by two different domestic cornpai.ies were compaired with one brand (Keflex) which was manufacrurea by Lilly pharmaceutical company, England. The plasma and urine cephalexin concentration were determined by microbiological assay (disk diffusion) using Sarcina LuteaATCC 9341 as test organism. Plasma and urine data were used to evaluate various pharmacokinetic parameters cephalexin including K,tl/':b C1/F, Vd/F, T max, CmaxAUC and F (relative). Results obtained from urinary data were supported the plasma data. The analysis of variance, to compare relative bioavailability and other pharmacokinetic parameters between tested samples were performed. These information indicates that there are no significant differences between the five different tested brands and they are bioequivalent. Therefore it can be suggested that brands (J.I,J.II,L.I,L.II) which formulated by domestic manufactures are bioequivalent and comparable to each other and to the one formulated by Lilly pharmaceutical company. 1842 Physiology THE ROLE OF ENDOTHELIUM DERIVED RELAXATION FACTOR (EDRF) IN VASCULAR TONE CONTROL Khoshbaten Ali 1 9 1996 3 1 180 180 27 11 2011 Ever since Thomas Lauder - Bruton First introduced Amylnitrate into clinical medicine, nitrovasodilators of different classes have been extensively used in the medical treatment of angina pectoris, myocardial infarction and heart failure. Understanding the mechanisms of action of nitrates has been greatly expanded in the last decade, particularly since the discovery of endothelium dependent relaxation and its mediator, the endogenous nitrate, NO. In present research, by using perfusion, isolated vessels 'ring (in-vitro) and laser Doppler flowmetry, (LDF) in-vivo techniques, the effect of some vasoactive substances and vascular nervous system were studied in present and absent of endothelium. Substances such as Adenosine, Adenosine triphosphate (ATP) and Acetylcholine (Ach) induced their vasodilation effect via endothelium. These responses were dose dependent. The vasoconstriction effect which followed, after nervous stimulation or vasoactive substances such as adrenergic agonists (clonidine, adrenaline and epinephrine) were augmented 60-100 percent, when NO. Synthesis was blocked by Nw-Nitro-I-arginine methyl-ester (L-NAME). This response was reversed by L-Arginine which induced NO synthesis. These results showed that ednothelium has role in modulation of vasoactivity of blood vessels due to stimulation of sympathetic nerves or endogenous substance in blood by releasing NO. 1843 Laboratory Sciences MOLECULAR MODELING AND RATIONAL DRUG DESIGN- A PERSPECTIVE Laczkowsky A. Meyer Edgar F. Swanson Stanley M. Kendra Worick R. 1 9 1996 3 1 181 181 27 11 2011 Enormous progress had been made in the study of biological macromolecule primarily due to two essential methods, X-ray crystallography and interactive computer graphics. The tools necessary to access and utilize these data are at our fingertips thanks to the World Wide Web and Internet. We here illustrate the use of the web by a beginning student and compare the results with experimentally determined structures of two human matrix metalloproteinases. We then discuss a facile graphics modelling program, PRONTO. Finally, we speculate on what science might be like when some of the current bottle-necks are removed. 1844 Laboratory Sciences CALORIES AND DESIGNER WATER Ladbury J.E. 1 9 1996 3 1 182 182 27 11 2011 Elucidation of how the thermodynamic parameters are determined by the molecular structures in a bimolecular interactions is becoming a fundamental driving force in the rational design of drugs. If we can determine the structure of the target and the potential drug we should be able to predict the equilibrium constant for their interaction based on simple relationships. With this information the temporally and financially expensive process of synthesis and affinity determination of lead compounds can be dramaticallyl~duced Using a series systems for which highly refined structural information is available the thermodynamic effect of interfacial water has been investigated. Based on this work we are able to draw conclusions on how water may be important in drug design. 1845 Pharmacology SROTPECER RECEPTORS AND THEIR POSSIBLE FUNCTION IN THE BRAIN Leonard B.E. 1 9 1996 3 1 183 183 27 11 2011 Thirty-three Years ago, Gaddum and Picarelli classified the serotonin receptors in the guinea pig ileum into D and M types based on the activity of dibenzyline (D) and morphine (M) to block contractions of intestinal smooth muscle caused by serotonin. The subsequent location of specific ligand binding sites for serotonin in the brain has led to the identification of ten serotonin receptor sub-types in rat brain. The cloning of these receptor sub-types has been of importance in enabling them to be classified as specific protein molecules encoded by specific genes. The problem now arises with regard to the linking of the changes in the cellular activity of the various receptor sub-types with the plethora of behavioural changes that arise as a consequence of the actions of serotonin in the brain. The present review summarizes the evidence implicating the role of specific serotonin receptor sub-types in sleep, anxiety states, schizophrenia and depression. A summary of the relationship between these receptor sub-types and their possible involvement in the aetiology of these diseases is also given. 1846 Pharmacology MODELING OF THE ALPHA SUBUNIT OF Gs PROTEIN AND ITS IMPLICATION IN THE UNDERSTANDING RECEPTOR-G PROTEIN COUPLING Mahmoudian M 1 9 1996 3 1 184 184 27 11 2011 1847 Hematology & oncology THE EFFECT OF DIFFERENT PHARRMACOLOGICAL AGENTS ON NK/LAK KILLING & TUMOUR CELL LINES PROLIFERATION Mansouri M. Nouri M.E. Oliver L.T.D. 1 9 1996 3 1 185 185 27 11 2011 The base of this study has been demonstrated the use of different drugs and dosages on different tumour cell lines and finally the effect of these drugs on natural killerllimphokine activated killer (NK/LAK) Killing. Tumour cells as target , mononeuclear cell activated with inter leukin-2(LAK) as effector, anti cancer drugs like tamoxifen , pentoxifylline , cycloheximide and cisplatin as stimulator or inhibitor of NK/LAK killing and colourimetric MT[ assay as evaluation agent. The different drugs with the similar dosages show stimulation or ingibition effect on NK/LAK killing. It is to be taken into concideration the possibility of metastasis of cancer is not unexpected. As the matter is important and needs more profound consideration , more studies and researches are currently being performed. 1848 Physiology VEIN FUNCTION, BIOMECHANICS AND LOCAL CONTROL MECHANISMS Monos E. 1 9 1996 3 1 186 186 27 11 2011 Many of the venous functions are biomechanical in their nature and/or related closely to biomechanical (hemodynamic) forces: 1 Blood conduits, collectors with flow-rectifying valves 2. Maintenance of filling pressure for the right heart by controlling venous return in the face of widely varying cardiac output arterial pressure buffer 3. Capacity function, redistribution of blood volume 4. Postcapillary resistance function 5. Transcapillary exchange of materials, selective barrier 6. Transmural transport 7. Angiogenesis 8. Synthesis of biologically active substances by the endothelium, smooth mucle cells and pericytes 9. Cooperation between venous endothelium and the PMNL-s (margination and rolling) 10 Inhibition of thromboembolic reactions 11. Supporting the orthostatic tolerance of the organism 12. An effector system of adaptation to whole body challenges 13. Special regional functions. Local mechanisms controlling venous biomechanics may include a.) mechanical, b.) hormonal, c.) ionic, d.) metabolic, and e.) neural processes. Biomechanical behavior of the veins was shown to alter adaptively in response to several other physiological factors and states, such as ambient temperature, pregnancy, age, body size, chronically increased gravitational load, as well as long-term physical exercise and even in certain pathophysiological conditions (e.g. experimental and human hypertension diseases). 1849 Biochemistry ALUMINIUM TOXICITY AND CHANGES IN SERUM PARAMETERS RELATED TO LIVER FUNCTION IN RATS Moshtaghie A.A Fazilati T.M. Amozadeh H. 1 9 1996 3 1 187 187 27 11 2011 The effect of aluminium on serum parameters related to liver function was investigated over different period of times. Serum lactate Dehydrogenase (LDH), Aspartate aminotrans­ferase (AST), Alanin aminotransferase (ALT) and total protein were chosen as indexes for liver function. Daily intraperitoneal administ­ration of 185 umoleslkg aluminium for 35 days elevated serum aluminium concentration from 10±0.5 to 668±81 f.lg/L. Short term administration of 740 umoleslkg of aluminium daily for 10 days elevated LDH, AST, ALT and bilirubin concentrations by 27%, 18%, 62% and 60% respectively in comparison to controls. Daily administration of 35, 185 and 370 umoleslkg of aluminium for 60 days elevated serum levels of LDH (33%, 47% and 69%), AST (29%, 34% and 70%), ALT (31%, 39% and 77%) and bilirubin (26% , 36% and 41%) respectively. Protein concentration was elevated significantly. Aluminium administration might disturb liver function by interferring with biochemical pathways. The interference of aluminium with parameters related to liver function has been discussed here. 1850 Radiotherapy CAN CIMETIDINE BE USED AS A RADIOPROTECTOR Mozdarani H. 1 9 1996 3 1 188 188 27 11 2011 An . in vivo micronucleus assay using mouse bone marrow for identifying radioprotective effect of cimetidine is described. The influence of cimetidine, an antagonist to histamine H2 receptor, on the kinetics of low and high LET radiations such as gamma rays and neutron induced micronuclei as well as the clastogenic effects of chemicals such as benzene, ara C and mitomycin C was tested in Swiss albino male mice. Cimetidine was administered at 15 mgjkg i.p 2 hours prior to irradiation to mice exposed to various doses of gamma rays and neutrons and single dose of drugs. Femoral marrow cells were analysed on slides stained with May-Giemsa. Frequency of micronucleated polychromatic erythrocytes (PCEs) and normochro­matic erythrocytes (NCEs) were determined at various time intervals after irradiation. Results obtained indicate that in all cases cimetidine reduced clastogenic effects of both low and high LET radiation by a dose reduction factor (DRF) of 1.5-2. The dose of cimetidine used in these experiments is not toxic for cells. The way in which cimetidine reduces clastogenic effects of radiation might be via radical scavaging mechanism. In order to verify this mechanism of action of cimetidine, protective effects of chemical agents such as benzene, sytosine arabinoside and' mitomycin C was also studied. These drugs produce biological effects via free radical formation. Results indicate that cimetidine show an anticlastogenic effect against these drugs. Radical scavanging mechanism of cimetidine is associated by amplification of glutathion system, DNA repair and cytochrome P450 inhibition. 1851 Pharmacology ROLE OF BETA RECEPTORS IN REPERFUSION INDUCED ARRHYTHMIAS IN INTACT RABBIT HEART Pandhi P. Shekhar A. Sharma D. 1 9 1996 3 1 189 189 27 11 2011 Coronary artery reperfusion which has become one of the important therapeutic interventions is associated with development of cardiac arrhythmias. The present investigation was carried out to study the role of beta receptor blocking agents with different properties on reperfusion induced ventricular arrhythmias in intact rabbit heart. After anaesthesia the rabbit hearts were subjected to 30 minutes coronary artery ligation followed by reperfusion for one hour. Three doses of propranolol (0.3, 1 and 3 mgfkg), metoprolol (0.5, 0.75 and 1 mg/kg) and pindolol (25, 50 and 100 ug/kg) were given 5 minutes before (pretreatment group) and at the time of reperfusion (treatment group) Propranolol exhibited 20-40% protection in pretreatment group and 33.3 to 66.6% protection in treatment group, with metoprolol, the protection was 33.3 to 66.6% (pretreatment) and 00 to 16.6% (treatment group). Pindolol offered 50 to 25% (pretreatment) and 16.6 to 33.3% (treatment group) protection. These results suggest a definite role of beta receptors in the pathophysiology of reperfusion induced arrhythmias. 1852 Pharmacology k CHANNEL AND CA CHANNEL CURRENTS AND THEIR INHIBITION BY GLIBENCLAMIDE IN SMOOTH MUSCLE CHLLS ISOLATED FROM GUINEA-PIG SEMINAL VESICLE Sadraei H. 1 9 1996 3 1 190 190 27 11 2011 Smooth muscle cells of seminal vesicle exhibit excitatcry junction patential on nerve stimulation and can fire evoked) action potential (1). However) the type of ion channels that underlie this electrical activity have not been described. I have investigated the type and pharmacology of ion channel in freshly isolated smooth muscle cells from the guinea-pig seminal vesicle using whole-cell patch-clamp technique. Two types of outward) k-current, and one type of inward Ca-Current are characterised. The first outward current had a transient appearance and was clearly distinguishable from the Ca-sensitive sustained current. The outward currents were classified on the basis of their voltage- and Ca-dependent and their sensitivities to block by TEA and 3,4- diaminopyridine. The inward current was also voltage-dependent) showed slow inactivation and was abolished by Cd and inhibited by nifedipine. The action of glibenclamide was also investigated because this compound had a surprising relaxant effect on the seminal vesicle. Glibenclamide (500p..M) inhibited both the transient and sustained current indicating an IC50 of about 60p..M. These experiments suggest that at least three types of ion channel are present in seminal vesicle smooth muscle: A-Type K channel, Ca-activiated K channel and li-type Ca channel. The observed inhibitory effect of glibenclamide on Ca channel current may be a mechanism underlying its relaxant effect on the whole tissue. 1853 Neurology Psychiatrics MODULATION OF SENSORY INOUT FROM THE HAND DURING VOLUNTARY MOVENT Sedgwick E.M. Weerasinghe V. 1 9 1996 3 1 191 191 27 11 2011 An early component of the somatosensory evoked potential, arising from the primary sensory cortex in man is attenuated during voluntary finger movement. The median nerve at the wrist was stimulated while the subject performed fractionated finger movements with the same hand. Subcortical components of the somatosensory evoked potential were not changed but the P25 cortical component was attenuated. Equivalent diapole analysis shows this component originates in areas 1 and 2 of the sensory cortex. It is proposed that the motor cortex (area 4) has an inhibitory pathway to areas 1 and 2 which is active during voluntary movements. 1854 Physiology THE EFFECT OF TETRODOTOXIN AND CADMIUM ON HIPPOCAMPAL NORADERNALINE AND 5-HYDROXYTRYPTAMINE RELEASE AND TURNOVER Vahabzadeh A. 1 9 1996 3 1 192 192 27 11 2011 Using the technique of in vivo microdialysis, we examined the relationship between neuronal firing and neurotransmitter release and metabolism in the hippocampus) The neurotoxin tetrodotoxin (TTX) was applied locally to block voltage-sensitive sodium channels) and extracellular Ca + + was replaced with cadmium (Cd + + ) to inhibit Ca + + dependant neurotransmitter release. The effectes of these drugs on both noradrenergic and serotonergic transmitter system were evaluated. The results show that 5-HT and NA release in hippocampal nerve terminal are active process and depend on the cell firing and influx of Ca + + ions prior to release. 5-HTand NA synthesis and turnover are also decreased by 1TX and Cd + +) these decays are greater in the absence of Ca + + ions. this suggest an essential role of ca + + ions for hippocampal monaoamine synthesis and turnover. 1855 Biochemistry QUALITATIVE AND QUANTITATIVE INVESTIGATION OF CELLULOLYTIC ENZYMES PRODUCED BY SOME AEROBIC FUNGI ISOLATED FROM MICROFLORA OF IRAN Yazdanparast R. Hamidi M. 1 9 1996 3 1 193 193 27 11 2011 The cellulolytic activities of eighteen aerobic fungi, isolated from the microflora of Iran, with respect to Avecil were compared with the cellulolytic activity of Trichoderma reesei, CBS 383.78. The data indicated that the majority of the isolated microorganisms were capable of hydrolysing Avicel in the solid agar media to a better extent than Treesei. However, the hydrolylic activities of the same test microorganisms in the liquid media containing A vecil were less than the relevant activity of T'Reesei. Thin-layer chromatography analysis of the products formed by each fungi from whatman filter o paper (no. 1) at 50 C for two hours of hydrolysis, were mostly consisted of small-size oligosaccharides, while the corresponding products formed by Treesei have higher molecular weights.