Effect of antihypertensive therapy on sympathetic nervous system activity in patients with essential hypertension

The sympathetic nervous system (SNS) plays a major role in blood pressure regulation. Although the exact relationship of the SNS to the etiology of hypertension remains undetermined, many of the agents used to treat hypertension interfere with this system. Clonidine, methyldopa, guanethidine, and reserpine decrease SNS tone whereas hydralazine, minoxidil, and hydrochlorothiazide increase it. Most evidence suggests that beta-adrenergic blocking agents decrease SNS activity. The effect of prazosin and captopril on the SNS requires further study. The appropriate use of these antihypertensive agents requires a knowledge of their sites of action and the physiological reflexes they induce. Efficacy, toxicity, and effective drug combinations can be predicted based on their mechanism of action and effect on SNS activity.     

Protein phosphorylation in respiring slices of guinea-pig cerebral cortex. Evidence for a role for noradrenaline and adenosine 3'':5''-cyclic monophosphate in the increased phosphorylation observed on application of electrical pulses.

1. Exposure of slices of cerebral cortex from guinea pigs to electrical pulses for 10s or to noradrenaline, 5-hydroxytryptamine or histamine increases the rate of phosphorylation of unidentified proteins in the tissue; the increases in protein phosphorylation due to electrical pulses and noradrenaline were non-additive, whereas the increases due to pulses and 5-hydroxytryptamine or histamine were additive. 2. The stimulating effects of electrical pulses and noradrenaline on protein phosphorylation were antagonized by the beta-adrenergic blocking agents L-propranolol, dichloroisoprenaline, practolol and ICI 66082, but not by the alpha-adrenergic blocking agents, phentolamine and phenoxybenzamine. 3. The increase in protein phosphorylation associated with electrical pulses was antagonized by 10 mum-trifluoperazine and 0.5 mum-prostaglandin E1. 4. It is postulated that under the experimental conditions used the action of electrical pulses on protein phosphorylation is mediated by noradrenaline acting through a beta-adrenergic receptor mechanism probably involving adenylate cyclase.     

Effective Inhibition of Ammonium Released from Heavily Contaminated Sediments through Selective Oxidation with Zeolite Layer

Abstract

In order to study the remediation effect of heavily contaminated sediments, the experiments to repair heavily contaminated sediments were carried out under selective and nonselective oxidation conditions. Results showed that a lot of denitrifying bacteria was detected on the surface of modified zeolite by fluorescence in situ hybridization (FISH) after inoculating both nitrifying and denitrifying bacteria for 7?days. Up to 3.69?mg/g, in-situ regeneration of ammonium on zeolite loading with high ammonium (ammonium adsorption: 4.20?m/g) was obtained, which was 1.42 times that of nonselective oxidation (2.60?mg/g). This indicated that the in-situ regeneration rate of zeolite under high ammonium adsorption (5.0?mg/g) and high bacterial inoculum (80?mL/g) was enhanced. Moreover, only 1.50?mg/L total nitrogen with 84% inhibition in the overlying water under selective oxidation conditions was observed, which was 2.37 times the inhibition percentage of modified zeolite under nonselective oxidation conditions. The results illuminated that effective inhibition of ammonium released from heavily contaminated sediments can be achieved through selective oxidation with zeolite layer. At the same time, the in-situ service life of attached biofilm-modified zeolite under selective oxidation conditions was 5.87?years, which was extended by 3?years compared with nonselective oxidation conditions.     

Beta-adrenergic-receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

Adrenergic receptor agonists are known to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of beta-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the beta-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of beta-adrenergic agonists on expression of the high affinity IL-2 receptors, [125I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of beta-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that beta-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites.     

Reduced risk of human lung cancer by selective cyclooxygenase 2 (COX-2) blockade: results of a case control study

We conducted a case control study of selective cyclooxygenase-2 (COX-2) blocking agents and lung cancer. A total of 492 newly diagnosed lung cancer cases were ascertained during January 1, 2002 to September 30, 2004, at The Ohio State University Medical Center, Columbus, Ohio. All cases were confirmed by examination of the pathology report. Healthy population controls without cancer were ascertained during the same time period. Controls were frequency matched at a rate of 2:1 to the cases by age, gender, and county of residence. We collected information on type, frequency, and duration of use of selective COX-2 inhibitors (primarily celecoxib or rofecoxib) and nonselective NSAIDs such as ibuprofen and aspirin. Estimates of odds ratios (OR) were obtained with adjustment for cigarette smoking, age and other potential confounders using logistic regression analysis. Odds Ratios for selective COX-2 inhibitors were adjusted for past use of other NSAIDs. Use of any selective COX-2 inhibitor for more than one year produced a significant (60%) reduction in the risk of lung cancer (OR=0.40, 95% CI=0.19-0.81). Observed risk reductions were consistent for men (OR=0.26, 95% CI=0.10-0.62) and women (OR=0.52, 95% CI=0.24-1.13) and for individual COX-2 inhibitors (OR=0.28, 95% CI=-0.12-0.67, for celecoxib and OR=0.55, 95% CI=0.19-1.56, for rofecoxib). Intake of ibuprofen or aspirin also produced significant risk reductions (OR=0.40, 95% CI=0.23-0.73 and OR=0.53, 95% CI=0.34-0.82, respectively), whereas acetaminophen, an analgesic with negligible COX-2 activity, had no effect on the risk (OR=1.36, 95% CI=0.53-3.37). This investigation demonstrates for the first time that selective COX-2 blocking agents have strong potential for the chemoprevention of human lung cancer.     

N-bromosuccinimide oxidation of a glucoamylase from Aspergillus saitoi

1. In order to elucidate the structure-function relation of a glucoamylase [EC 3.2.1.3, alpha-D-(1 leads to 4) glucan glucohydrolase] from Aspergillus saitoi (Gluc M1), the reaction of Gluc M1 with NBS was studied. 2. The tryptophan residues in Glu M1 were oxidized at various NBS/Gluc M1 ratios. The enzymatic activity decreased to about 80% of that of the native Gluc M1 with the oxidation of the first 2 tryptophan residues. The oxidation of these 2 tryptophan residues occurred within 0.2-0.5 s. On further oxidation of ca. 4-5 more tryptophan residues of Glu M1, the enzymatic activity of Gluc M1 decreased to almost zero (NBS/Gluc M1 = 20). Thus, the most essential tryptophan residue(s) is amongst these 4-5 tryptophan residues. 3. 7.5 tryptophan residues were found to be eventually oxidized with increasing concentrations of NBS up to NBS/Gluc M1 = 50. This value is comparable to the number of tryptophan residues which are located on the surface of the enzyme as judged from the solvent perturbation difference spectrum with ethylene glycol as perturbant. 4. In the presence of 10% soluble starch, about 5 tryptophan residues in Gluc M1 were oxidized at an NBS/Gluc M1 ratio of 20. The remaining activity of Glu M1 at this stage of oxidation was about 76%. On further oxidation, after removal of soluble starch, the enzymatic activity decreased to zero with the concomitant oxidation of 2 tryptophan residues. The results indicated that the essential tryptophan residue(s) is amongst these 2 tryptophans. 5. The UV difference spectrum induced by addition of maltose and maltitol to Gluc M1 showed 4 troughs at 281, 289, 297, and 303 nm. The latter 3 troughs were probably due to tryptophan residues of Gluc M1 and decreased with NBS oxidation.     

Calmodulin, activated cyclic nucleotide phosphodiesterase, microtubules, and vinca alkaloids

Calmodulin 1.8 and 10.6 microM, inhibited the polymerization of bovine brain microtubules by 30 and 50%, respectively. Two 55,000- to 68,000-dalton calmodulin-binding protein as well as calmodulin-dependent and -independent phosphodiesterases (PDE) were found associated with microtubule proteins. Among the antimicrotubule drugs, such as colchicine, podophyllotoxin, griseofulvin, and vinca alkaloids (vinblastine, desacetylvinblastine amide, and vincristine), the vinca alkaloids were selective inhibitors of calmodulin-activated PDE activity. This action of vinca alkaloids resides in the catharanthine moiety of vinblastine molecule. An alpha 2 inhibitor, yohimbine, affects the microtubules, and a series of alpha-adrenoceptor blocking agents were examined for their effects on calmodulin-dependent PDE. The relative order of the potency is phenoxybenzamine = dibenamine greater than phentolamine greater than yohimbine greater than prazosin greater than tolazoline, and the first four drugs in this series were selective inhibitors of calmodulin action. Inasmuch as phenoxybenzamine and dibenamine are alkylating agents, the effects of antineoplastic alkylating agents on the calmodulin action were also examined. Busulphan, melphalan, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and streptozotocin (up to 4 mM) were not selective inhibitors of calmodulin action. Maytansine, a vinca alkaloid-type antimicrotubule agents as well as an alkylating agent, selectively inhibited the calmodulin with a potency similar to vincristine. In addition, phenoxybenzamine affected Ca2+-dependent fluorescence induced by the interaction between calmodulin and hydrophobic fluorescent probes, whereas vinblastine was ineffective. However, the binding of vinblastine to calmodulin is calcium dependent. Studies such as these suggest the importance of physical and structural considerations in drugs binding to calmodulin as well as at least two different binding sites for drugs on calmodulin.     

Lipolysis in rat adipose tissue in vitro and its alpha 2 adrenergic control

Although the alpha 2-adrenergic inhibitory control on lipolysis in several mammalian species, e.g. in dogs, hamsters, rabbits and also in man has been proved recently, in rats some peculiarities have been described in the alpha-adrenergic regulation of lipid mobilization. In the present study the effect of the specific alpha 2-adrenergic blocking agent--yohimbine (YOH)--on lipid mobilization in young (45-55 days old) and old (6 months) rats of the Wistar strain was followed and also its interaction with the beta-adrenergic blocking agent propranolol and the specific alpha 2-adrenergic agonist--clonidine. Furthermore, the effect of YOH on the isoprenaline (ISO) induced lipolysis was studied. The adipokinetic effect was estimated from the amount of released non-esterified fatty acids from the tissue preparation into the incubation medium. In all experimental series YOH produced a significant response, which was concentration-dependent (pD2 6.2) with the maximum effect corresponding to 40% of the highest adipokinetic action of ISO. Young rats were more sensitive than old animals. In both age groups YOH non-competitively decreased the highest effect of ISO to the level of its own lipid-mobilizing activity. In the presence of YOH, the ISO dose-response curve therefore completely disappears. The adipokinetic effect of YOH can be antagonized competitively by clonidine (CLO) (pA2 6.25 and 6.01 for concentrations of CLO 1 and 10 mumol.1(-1) respectively). The inhibitory effect of propranolol is about two orders lower. It is concluded that in rats the alpha 2-adrenergic control rather concerns basal lipolysis, whereas induced lipid mobilization can be inhibited by depression of the alpha 2-activity.     

A comparison of catecholamine-induced internalization of beta-adrenergic receptors and receptor-mediated endocytosis of epidermal growth factor in human astrocytoma cells. Inhibition by phenylarsine oxide

The ligand-induced internalization of beta-adrenergic receptors and the receptor-mediated internalization of epidermal growth factor were blocked, under similar conditions, by phenylarsine oxide (PAO) in human astrocytoma cells (1321N1). The inhibition was not prevented or reversed by monofunctional sulfhydryl agents such as 2-mercaptoethanol or glutathione; however, the inhibitory action of PAO was blocked and reversed by bifunctional thiols such as 2,3-dimercaptoethanol or dithiothreitol. The results are consistent with the interaction of PAO with vicinal sulfhydryl groups to form a stabile ring structure. PAO did not prevent isoproterenol-induced uncoupling (desensitization) of beta-adrenergic receptors even though receptor internalization was completely blocked. The effects of PAO on receptor internalization could not be explained by any action of the trivalent arsenical to lower ATP levels. Ligand binding to both receptors was not detectably altered by PAO under conditions selective for inhibition for endocytosis. The results suggest a common mechanism for internalization of beta-adrenergic receptors and epidermal growth factor by a process that involves vicinal sulfhydryl groups.     

Sympathetic control on salivary secretion by the parotid gland in rabbit. I. Effects on the unstimulated gland (author's transl)]

The sympathetic influences on the rabbit unstimulated parotid gland were studied. The experiments were carried out in anaesthetized rabbits with the Stenon aduct cannulated. Direct stimulation of the superior cervical ganglion elicits variable salivary flows. The high amylase content in the saliva points to a sympathetic secretory action upon acinar cells. The administration of alpha-adrenergic blocking agents (dihydroergotamine, phentolamine and phenoxybenzamine) clearly reduces and even abolishes the effect of the sympathetic stimulation upon flow. The administration of a beta-adrenergic blocking agent (propranolol) slightly reduces the sympathetic action. However the amylase activity is greatly reduced. All this suggests that the secretory effects on the fluid fraction should predominantly be alpha-adrenergic while on the secretion of enzymes the beta-receptors should play an important role.     

In vitro assessment of the selectivities of various beta-adrenergic blocking agents

Intrinsic sympathomimetic- and membrane activities of beta-adrenoceptor blocking agents are of little or no clinical significance. A selective blockade of cardiac receptors has important therapeutic consequences, especially in the treatment of patients with obstructive airways diseases. Profound depression of miocardial contractility can be deleterious in patients with cardiac muscle damage and the use of beta-adrenergic blockers with a quantitative selectivity towards chronotropism may become an important consideration. The effects of a number of beta-sympatholytics have been determined on isolated cardiac preparations (beta₁-adrenergic receptors) and tracheal preparations (beta₂-adrenergic receptors) of guinea-pigs. Results indicate that prindolol is the most selective blocker of the beta₁ chronotropic receptors whilst atenolol could be classified as being the most cardioselective beta-adrenergic blocker investigated. Butoxamine, on the other hand, proved to be the most beta₂-selective one.     

Interactions of Lycopodium alkaloids with acetylcholinesterase investigated by 1H NMR relaxation rate

In order to further understand the interaction processes between the Lycopodium alkaloids and acetylcholinesterase, the binding properties of N-acetyl huperzine A (1), huperzine B (2) and huperzine F (3) with Torpediniforms Nacline acetylcholinesterase (TnAchE) were investigated by 1H NMR methods. The nonselective, selective and double-selective spin-lattice relaxation rates were acquired in the absence and presence of TnAchE at a ratio of [ligand]/[protein]=1:0.005. The selective relaxation rates show protons of 1-3 have dipole-dipole interaction with protons of TnAchE at the binding interface. The molecular rotational correlation time of bound ligands was calculated by double-selective relaxation rate at 298 K, which showed that 1-3 had high affinity with the protein. The results indicate that investigation of 1H NMR relaxation data is a useful method to locate the new Lycopodium alkaloids as AchE inhibitors.     

Comparison of propranolol,metoprolol, and acebutolol on insulin-induced hypoglycaemia.

Metoprolol and acebutolol, two supposedly cardio-selective beta-adrenergic recptor blocking agents, were tested in healthy volunteers against propranolol, a non-selective drug, for their effect on blood glucose levels during insulin-induced hypoglycaemia. There was not significant difference between propranolol and metoprolol, which both potentiated the initial hypoglycaemic action of the insulin and delayed the return to normoglycaemia. Acebutolol, even though potentiating the initial hypoglycaemia, did not possess a significant delaying effect. A similar trial should be undertaken in diabetics to determine with certainty the safety of such drugs in diabetes mellitus.     

Analogues of arginine vasopressin modified in the N-terminal part of the molecule with enantiomers of N-methylphenylalanine.

Four new analogues of arginine vasopressin (AVP) substituted in positions 2 and 3 with all possible combinations of enantiomers of N-methylphenylalanine were synthesized and studied to assess the influence of N-methylation of the peptide bonds between the first three amino acids on the pharmacological properties of the resulting peptides. The next three analogues were designed to learn how the shortening of the peptide chain, by removal of one of the N-methylphenylalanine residues, would affect pharmacological properties of the resulting compounds. The activity of the analogues was tested in the in vitro uterotonic, pressor and antidiuretic tests. None of the prepared analogues displayed significant biological activity with the exception of [Me-d-Phe(2), Me-Phe(3)]AVP and [Me-d-Phe(2,3)]AVP, which showed low antiuterotonic activity (pA(2) = 6.6 and pA(2) = 6.4, respectively). Our results, while not impressive in terms of biological activity, may be helpful for designing potent and selective oxytocin antagonists.     

Inhibition of epinephrine-induced lipolysis in isolated white adipocytes of aging rabbits by increased alpha-adrenergic responsiveness.

The aim of this study was to explain the unresponsiveness of rabbit perirenal adipose tissue to epinephrine. The in vitro lipolytic response to isoproterenol and to epinephrine alone or associated with alpha- or beta-adrenergic blocking agents, was studied in the adipocytes of rabbits of various ages. Epinephrine induces a large glycerol release in young rabbit adipocytes whereas an increase in the rate of lipolysis cannot be shown with adult rabbit fat cells. Moreover, an antilipolytic effect can be shown for low concentrations of epinephrine when the basal rate of lipolysis is high in older rabbit adipocytes. Isoproterenol (beta-adrenomimetic) always exerts a strong adipokinetic effect, thus revealing functional beta-receptor sites. The blockade of alpha-adreneoceptor sites by phentolamine, which has no effect on young rabbits, abolishes the antilipolytic effect and unmasks strong lipolytic effect of epinephrine on aged and normal rabbit adipocytes. The loss of beta-adrenergic responsiveness towards epinephrine in the aging rabbit is linked to the involvement of an increased alpha-adrenergic responsiveness. The stimulation of alpha receptor sites by epinephrine leads to a depressive effect on lipolysis (lack of adipokinetic effect or antilipolytic action).     

Characterization of the subtype of muscarinic receptor coupled to the stimulation of phosphoinositide hydrolysis in 132-1N1 human astrocytoma cells.

Stimulation of muscarinic receptors increases phosphoinositide (PI) hydrolysis in 132-1N1 human astrocytoma cells. To evaluate the subtype of receptors which mediate PI hydrolysis in 132-1N1 cells, the effects of: a) the nonselective M1 agonist, carbachol; b) the selective M1 agonist, 4-hydroxy-2-butynyl-trimethylammonium chloride-m-chlorocarbinilate (McN-343); c) the nonselective antagonists, atropine and scopolamine; d) the relatively selective M1 antagonist, pirenzepine; e) the relatively selective M2 antagonists, AF-DX 116 (11-2-diethylaminomethyl-1-piperidinylacetyl-5, 11-dihydro-6H-pyrido-2,3-b-1,4-benzodiazepine-6-one) and methoctramine and f) the relatively selective M3 antagonist, hexahydrosila-difenidol (HHSiD) on PI hydrolysis in 132-1N1 cells were studied. The cell pools of inositol-phospholipids were prelabelled by incubating 132-1N1 cells in a low inositol containing medium (CMRL-1066) supplemented with [3H]inositol (2 microCi/ml) for 20-24 hours at 37 degrees C. The cells were washed and resuspended in a physiological salt solution, and PI hydrolysis was measured by accumulation of [3H]inositol-1-phosphate (IP) in the presence of 10 mM LiCl. Carbachol produced time and concentration dependent PI hydrolysis (EC50, 37 microM). McN-A343 did not cause significant hydrolysis of PI in 132-1N1 cells indicating that the receptor was not of M1 type. All the above muscarinic antagonists caused a concentration dependent decrease in the level of IP in response to carbachol (100 microM). The rank order of their affinities (pA2 values) was: atropine (8.8) > HHSiD (7.6) > pirenzepine (6.8) > methoctramine (6.0) > AF-DX 116 (5.8). This rank order supports the concept that M3 (other names, M2 beta, glandular M2) receptors are linked to PI hydrolysis in 132-1N1 cells. HHSiD, which is selective for M3 receptors of the smooth muscle has higher affinity for muscarinic receptors in 132-1N1 cells than AF-DX 116 which is selective for M2 receptors in cardiac tissue. If the receptor in 132-1N1 cells had been M2, part of the rank order for affinities would have been methoctramine > AF-DX 116 > HHSiD > pirenzepine. From all of these observations, the muscarinic receptor for PI hydrolysis in 132-1N1 cells is tentatively characterized as of M3 type.     

Cancer prevention with food factors: alone and in combination

Cancer prevention strategies making use of combined agents with distinct molecular mechanisms, rather than individual agents, are considered promising for higher efficacy and lower toxicity. Although there is increasing understanding of the synergistic combinations of synthetic agents, our knowledge regarding such combinations of food factors remains limited. We recently found that free radical generation suppressants from food items in combination with their scavengers at low concentrations exhibited notable synergistic effects in activated leukocytes, whereas combinations of agents with similar modes of action showed additive or antagonistic effects. For example, pound -)-epigallocatechin gallate (EGCG) from green tea has been shown to increase the endotoxin-induced production of proinflammatory mediators such as prostaglandin E(2) and tumor necrosis factor-alpha in RAW264.7 macrophages, whereas the soybean isoflavonoid genistein compensated for these inverse properties of EGCG, leading to marked suppression in combination. The present review briefly highlights the potential effectiveness of combinations of several agents with anti-oxidative and anti-inflammatory properties for cancer preventive strategies.     

Influence of ashing techniques on the analysis of trace elements in animal tissue

A multitude of methods exists at present for the solubilization of biological tissues for atomic absorption analysis. We have examined several common methods of wet ashing using NBS bovine liver in order to determine which acids, acid combinations, or bases should be used as digesting agents for accurate and precise measurement of iron, copper, zinc, and manganese. Nitric acid proved to be the most effective wet ashing agent. With nitric acid, mean concentrations for iron, copper, and zinc differed from NBS certified values by less than 1.5% while those for manganese differed by 4%.     

Ontogeny of cholinergic and adrenergic cardiovascular regulation in the domestic chicken (Gallus gallus)

Adrenergic and cholinergic tone on the cardiovascular system of embryonic chickens was determined during days 12, 15, 19, 20, and 21 of development. Administration of the muscarinic antagonist atropine (1 mg/kg) resulted in no significant change in heart rate or arterial pressure at any developmental age. In addition, the general cardiovascular depressive effects of hypoxia were unaltered by pretreatment with atropine. In addition, the ganglionic blocking agent hexamethonium (25 mg/kg) did not induce changes in heart rate. The beta-adrenergic antagonist propranolol (3 mg/kg) induced a bradycardia of similar magnitude on all days studied, with a transient hypertensive action on days 19-20, indicating the existence of an important cardiac and vascular beta-adrenergic tone. Injections of the alpha-adrenergic antagonists prazosin or phentolamine (1 mg/kg) reduced arterial pressure significantly on all days of incubation studied. Collectively, the data indicate that embryonic chickens rely primarily on adrenergic control of cardiovascular function, with no contribution from the parasympathetic nervous system.     

Molecular targets for existing and novel immunosuppressive drugs

Anti-neoplastic cytostatic antiproliferative agents, such as methotrexate, 6-mercaptopurine and cyclophosphamide, were originally used as immunosuppressive drugs. Although these agents induced only modest anti-rejection activity, they caused serious non-specific bone marrow suppression, impairing host resistance and increasing the incidence of infections. Unlike these non-selective agents, cyclosporine A, tacrolimus and sirolimus act more selectively on different stages of the T-lymphocyte (T-cell) and B-lymphocyte (B-cell) activation cycles; however, cyclosporine and tacrolimus are nephrotoxic, whereas sirolimus causes hypertriglyceridaemia. Thus, despite this progress, continued efforts must be made to develop and test new, potentially very selective agents. The agent 15-deoxyspergualin moderately inhibits both mitogen-stimulated T-cell proliferation and the generation of cytotoxic T lymphocytes (CTLs) but does not affect the production of interleukin 2 (IL-2). Another drug, FTY720, has a unique action to prevent rejection, by altering the homing of lymphocytes to the lymphoid compartments. The newest members of the family of antiproliferative agents, namely mycophenolate mofetil, leflunomide and brequinar, are potentially more selective than their predecessors. However, the most promising agents are produced using antisense technology. This approach involves the design of antisense oligodeoxynucleotides; these novel drugs are designed to block allograft rejection by blocking selected messenger RNA (mRNA). This review outlines the mechanisms of action, the limitations of application and the molecular or cellular targets of traditional agents, newly developed drugs and also antisense technology, which is an example of a new application of molecular medicine.