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Simvastatin

Simvastatin

By Z. Tjalf. Princeton University. 2019.

It could be accomplished by the help of the following two cardinal modifications discount simvastatin 20 mg otc, namely : (a) Need for a continuous change in wavelength so that light through the blank and through the sample may be monitored continuously 20mg simvastatin with mastercard, and (b) Measurements done with a recording spectrophotometer purchase simvastatin 10mg on-line. The above two modifications have been duly incorporated in a double-beam spectrophotometer. In fact, the source beam is usually split in two different manners, namely : (a) Separated in Space : In this instance, the source beam is split between the sample cell-path and the reference cell-path, and finally detected by two diode detectors. Here, the two detectors should be adequately matched so that no changes occur relative to each other during the measurements, (b) Separated in Time : In this case, the source beam is split with the help of an optical chopper which permits the source beam to alternate between the sample cell-path and the reference cell- path. Here, the source should be stable enough so that no changes take place in the radiant energy during the chopping time. Keeping in view, this specific, rigid and stringent requirement, the separation-in-space method is found to be normally of lower precision and accuracy than the separation-in time-method. Evidently, the optical choppers are quite expensive, and therefore, the instrument manufacturers very often utilize the separation-in-space method for the routine measurement spectrophotometers. However, the most sophisticated double-beam spectrophotometer is usually pretty expensive by vir- tue of the following facts, namely : (i) Greater operating stability, (ii) Rapid speed compared to single-beam instruments, (iii) Complicated optical system involved, and (iv) Recording device for recording absorbance Vs wavelength. These instruments are mostly based on microcomputer-controlled devices with built-in recorder to accom- plish faster speed and greater operating stability. Extinction is solely dependent upon the following two factors, namely : (a) Concentration of the absorbing substance present in the solution, and (b) Thickness of the absorbing layer taken for measurement. Bearing in mind the ease in calculations and also the convenience of reference, the extinction of a 1-cm layer of a 1% w/v solution is usually recommended in most of the official compendia (i. This particular property is the basis for most assay methods included in pharmacopoeia that are absolutely free from interfering materials, besides being utilized for identifying substances. In actual practice, where a test or an assay recommends the usage of a Reference Substance, the spectrophotometric measurements are always performed first with the solution prepared from the Reference Substance by the directions provided in the specific monograph and then with the corresponding solution prepared from the substance under examination. Nevertheless, the second measurement must be done immediately after the first, by employing the same cell and the same instrumental parameters. Importantly, when a double bond recording instrument is being employed the solvent cell is always placed in the reference beam. Particular care must be taken to employ solvents free from contaminants absorbing in the specific spectral region being used. In measuring the extinction of a solution at a given wavelength, the extinction of the solvent cell and its contents must not exceed 0. Particularly, the solvent in the solvent cell should always be of the same purity, grade and batch as that employed to prepare the respective solution and above all it must be free from fluorescence at the wavelength of measurement. All the measure- ments are normally performed with reference to the solvent used to prepare the solution being examined, unless otherwise indicated in the individual monograph. In tests for identification, a recording instrument is always preferred ; besides, the concentration of the solution and the path-length are specifically monitored. In case, the laid down conditions are not suitable for a particular instrument, the thickness of the solution (i. Now, transfer 10 ml of this solution into a 100 ml volumetric flask, add 10 ml of buffer solution pH 9. To tube 1 add 10 ml of imidazole-mercury reagent, mix, stopper the tube and immerse it in a water-bath previously maintained at 60 °C for exactly 25 minutes, with occasional swirling. Calculations : The content of C16H19N3O5S may be calculated from the difference between the extinctions of Solution-1 and that of Solution-2 and from the difference obtained by repeating the operation using 0. Cognate Assays : Ampicillin can also be assayed by employing the above method using 0. The primary aromatic amino group present in the latter is subsequently diazotized in the usual manner and coupled in acidic solution with N-(1-naphthyl)-ethylenediamine hydro- chloride in the absence of light (caution). To an aliquot of the resulting acetic acid solution an excess of phenoldisulphonic acid is added to produce a yellow colour which is subsequently intensified by adding an excess of ammonia. Materials Required : Glyceryl trinitrate tablets : 20 ; glacial acetic acid (90% v/v) : 5 ml ; phenoldisulphonic acid solution (heat 3 g of phenol with 20 ml of sulphuric acid on a water-bath for 6 hours, and transfer the resulting liquid to a stoppered vessel) : 2 ml ; strong ammonia solution ; 20 ml ; potassium nitrate (previously dried at 105 °C) : 1 g ; Procedure : Weigh and powder 20 tablets. To 2 ml of the supernatant liquid add 2 ml of phenoldisulphonic acid solution and allow to stand for 15 minutes. Finally, measure the extinction of a 1-cm layer of the filtrate at 405 nm, as described earlier, employing as blank 2 ml of glacial acetic acid, treated exactly in a similar fashion, begin- ning at ‘‘add 2 ml of phenoldisulphonic acid solution......... Taking 2 ml of this solution, just repeat the assay beginning the procedure at ‘‘add 2 ml of phenoldisulphonic acid solution...... Cognate Assays : The following two pharmaceutical products, namely : Pentaerythritol tetranitrate Tablets and Diluted Isosorbide dinitrate are assayed by using a solution of phenoldisulphonic acid as detailed below : S. Now, measure the extinction of the irradiated solution at the maximum at about 418 nm as described earlier. Give a brief and comprehensive account of the following terminologies : (a) Electromagnetic spectrum, (b) Molar absorptivity, (c) Absorption spectra, (d) Structural features, and (e) Absorption bands. Discuss the theory, procedure and calculations for the assay of the following medicinal compounds : (i) Folic acid, (ii) Glyceryl trinitrate tablets, and (iii) Trans-Diethylstilbesterol. It also serves as a powerful ‘analytical tool’ for the extensive and intensive study of molecular structure. In fact, infrared absorption spectra are due to changes in vibrational energy accompanied by changes in rotational energy. In usual practice, however, either the wavelength (µ) or the wave number (cm–1) is employed to measure the position of a given infrared absorption. More precisely, the infra- red regions may be categorized into three distinct zones based on their respective wave numbers and wave- lengths as stated below : S. Far Infrared 667-50 15-200 Besides, the infrared region is found to be normally rich in peaks by virtue of the fact that there exist a number of vibrational modes (3n-6, where, n = number of atoms for any nonlinear molecule). Example : The C = O stretching frequency is about 1700 cm–1 ; whereas the C—H stretching frequency is about 3000 cm–1 and both of them are almost independent of the rest of the molecule as depicted in Table 22. Example : The C—C stretching frequency depends largely on what else is bonded to the carbon atoms. It is interesting to observe here that this particular region of the spectrum is densely populated with bands. As we know that no two ‘fingerprints’ could be identical in human beings, exactly in a similar manner no two compounds may have the same ‘fingerprint region’. Thus, each and every molecule essen- tially gives rise to a unique spectrum which offers a characteristic feature of the same. Therefore, it would be necessary to have a clear concept of various modes of vibrations often encoun- tered in different molecules having a variety of functional moieties, laws governing them and the mathemati- cal derivations related to them. Rather it may be regarded as a sort of flexible system comprising of balls of varying masses representing the atoms of a molecule and springs of varying strengths representing the chemical bonds of a molecule. The vibrations for molecules are of two types, namely : (a) Stretching, and (b) Bending (or deformation). Stretching Vibration causes stretching whereby the distance between the two atoms increases or decreases, but the atoms remain in the same bond axis. Bending (or Deformation) Vibration causes bending whereby the position of the atom changes relative to the original bond axis. Therefore, the various stretching and bending vibrations of a bond usually take place at particular quantized frequencies.

On the same line of reasoning simvastatin 20 mg visa, pep- tide drugs would have fewer drug–drug interactions purchase simvastatin online pills, although order simvastatin 20mg without a prescription, as previously stated, they have an increased risk of immunogenic effects. Considering that peptide drugs are large molecules composed mainly of natural amino acids with high target speci- fcity and are easily degraded by peptidases, peptide drugs would in theory exhibit lower toxicity than small drug molecules. Likewise, considering that peptide drugs have diffculty crossing membranes, they are less likely to accumulate in tissues and thus have a lower risk of adverse drug reactions over time. The sheer largeness of peptide drugs also means that they are more biologically and chemically diverse. In actual practice, however, peptide drugs are often used to derive small nonpep- tide drug molecules. Doing so offers the benefts from both classes and the fne line that differentiates between a peptide drug and small drug molecule becomes faded. Indeed, after a lengthy process of rational drug design where residues are changed from natural amino acids to nonnatural amino acids then to nonamino acids, it becomes rather challenging at times to classify if a drug is peptide or nonpeptide. Although we would like to classify a nonpeptide drug as a compound that does not possess any amino acid, out of respect for the developers of the drugs, in this chapter, we will keep the nonpeptide or peptide assignments that the drug developers have chosen, and will thus avoid any debate over semantics. We will focus on success- ful stories of peptide-derived drugs that are processed by enzymes. We will try to be as up-to-date as possible in the information that we provide at the time that this chapter is being written. It should be noted that, in this chapter, most comparisons done between differ- ent drugs are restricted to our own personal viewpoint; because of legal reasons and personal pride, the drug developers would claim originality to their own discoveries. Hence, we would like the readers to read with an open mind and come up with their own interpretations of the information that we provide. During the process of changing a peptide drug to a peptide-like drug and eventually to a nonpeptide drug, the naming of each residue becomes confusing because two or more residues may be merged into one functional structure. We will be using the Schechter and Berger [1] nomen- clature that assumes that the substrate binds to the active site of an enzyme in an extended backbone conformation. Within the active site, subsites, also referred to as pockets, ′ are denoted as Sn and Sn, where n represents the number of subsite away from the catalytic S1 subsite, with the prime symbol denoting the opposite direction. Often, N-terminal residues are referred as Pn, whereas C-terminal ′ residues are referred as Pn. The naming of peptide drugs follows the same rules as ′ ′ that of peptide substrates. For example, P2–P1–P1–P2 is a tetrapeptide drug with a ′ scissile bond between the P1 and P residues. For peptide inhibitors, the inhibitory 1 unit, which is the unit that prevents enzyme cleavage, is assigned to the P1 residue. One should keep in mind that because the numbering is based on the subsites of the active site rather than the sequential order of the residues of the peptide drug, and that the chemical structures of the enzyme and peptide drug are three-dimensional by nature, that in some cases, the numbering of the residues of the peptide drug may not follow a sequential order. In simpler words, there are cases where the peptide drug does not bind to the active site in an extended backbone conformation. An example of an irregular order numbering is argatroban, a direct thrombin inhibitor, which has aP3–P1–P2 sequence (Section 5. Hence, it is often easier to commercialize natural enzymes or activators of enzymes found in nature, and to develop inhibitors of enzymes, than to create more potent enzyme activators. A philosophical reasoning for this observation could be that nature has selected the best enzymes and their activators, whereas man can only copy or destroy nature’s refnements. Despite the previous statement, researchers have designed a few enzyme activators, such as α-methyldopa and droxidopa (Section 5. Here, we are loosely equating the term enzyme activator to substrate, because as far as we are aware, there is no allosteric activator in the pharmaceutical market. Most activators of enzymes, or the enzymes themselves, are developed via either extraction of pharmacologically active natural substances from a crude inexpensive natural source or by replicating the natural substances by synthetic means. On the contrary, most potent inhibitors of enzymes are derived from natural lead compounds, or from natural substrates that have been corrupted to become enzyme inhibitors. From our own experience, the frst step in substrate-based drug design of modula- tors is to establish an assaying system for enzyme activity. A modulator is either an activator or inhibitor, which in our case, applies to a substrate or its peptide inhibitor. As the initial step, a reproducible enzyme activity assay system must be developed from a substrate and enzyme that both must be stable and pure. It is noteworthy that the enzyme often can process several different substrates and the choice of substrate, especially in substrate-based design of enzyme inhibitors, will determine the structural outcome of the derived modulators. In order to improve the processing effciency of the substrate by the enzyme, the substrate and enzyme may be structurally altered by synthetic means to improve purity and stability, so as to reduce variations between experiment results. Often, the fnal substrate used in the assay is a shortened yet active version of a natural substrate, and the enzyme is modifed from its natural form to prevent self-digestion. Any drastic change from the natural substrate or enzyme could be viewed by the scientifc community as a huge leap from the substrate and the natural form of the enzyme, and thereby negatively refecting on the research as a false image of nature. A common method of substrate-based design of inhibitors entails the introduc- ′ tion of an inhibitory unit near the scissile bond, between the P1 and P1 residues of the substrate. The inhibitory unit is a modifed version of the P1 residue of the substrate such that the enzyme can recognize and bind to the inhibitory unit at the catalytic site, but the enzyme cannot readily cleave the inhibitor. A common mech- anistic feature of protease inhibitors is the presence of a transition state isostere, as a part of the inhibitory unit, to simulate the transition state of amide bond hydrol- ysis, as depicted in Figure 5. B from enzyme from enzyme Transition state mimetic inhibitor Pro N H O O O H H O O − O N N H O H O Figure 5. Our recent studies combined neutron diffraction crystallography to conclusively pro- vide direct experimental evidence of the catalytic mechanism of the protease and its inhibition by the inhibitory unit [5]. In the initial design of protease inhibitors, other than the central inhibitory unit, the remaining residues of the inhibitor are kept similar to that of the substrate. In simpler words, the inhibitor is a mimic of the substrate and cannot be processed by the enzyme. If the enzyme can cleave the inhibitor, albeit at a slower rate, or if the inhibitor can be washed out over time, the inhibition is considered reversible. If the inhibitor forms strong interactions with the enzyme to the extent that the inhibitor cannot be removed until the enzyme is degraded, then the inhibition is irreversible. If an unforeseen adverse drug effect is observed with an inhibitor, the adverse effect is expected to be more prolonged in an irreversible inhibitor than a reversible inhibitor. Hence, due to safety concerns associated with mammalian enzymes, the design of reversible inhibitors is often preferred over that of irreversible inhibitors. However, when it comes to nonmammalian enzymes, such as those of viruses and parasites, irreversible inhibitors may be favored over reversible inhibitors, in order to eliminate completely and quickly the viral or parasitic threat, once it has been ascertained that there is absolutely no chance of recognition by other mammalian host enzymes. Following the introduction of the inhibitory unit in the design, several attempts are performed to minimize the peptide nature of the molecule to avoid most peptide-associated problems that we have discussed in the introduction (Section 5. Of course, for the case of substrate-based design of activators, an inhibitory unit is obviously not introduced. During the ensuing rational drug optimization process, quantitative structure–activity relationship studies are performed to statistically confrm and suggest any potency trend observed in modulatory activity. The peptide drug is truncated to reduce size-related pharmacodynamic and pharmacokinetic problems.

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Asiam inherited his chemical shop simvastatin 10mg with visa, a converted space attached to his home purchase generic simvastatin pills, from his father and was a licensed chemical seller for nearly 20 years prior to his conversion to CareShop purchase simvastatin overnight. Commenting on the difer- ence between his business before and after conversion, Mr. Asiam spent roughly $200 on improvements, which include ceiling fans, a refrigerator, and glass display cases. They might also consider developing chains of supervision wherein minimally educated staff manage stock and then report their needs up to someone who is qualifed to identify good-quality wholesalers and buy from them. The committee believes that national pharmacy councils are best able to articulate what the proper reporting chain should be in their country and what minimum qualifcations their countries’ patients will accept. The minimum training for a drug dispenser or pharmacy technician in rural Canada will be dif- ferent from what is suitable to rural Nepal. In any case, there should be emphasis on vocational training to credential medicine shopkeepers and include them in the health system. There is evidence that task shifting can alleviate the pharmacist short- age in developing countries. In Malawi, an emergency training and cre- dentialing program for health workers increased the number of pharmacy technicians by 84 percent between 2004 and 2009 (O’Neil et al. Malawian pharmacy technicians supervise pharmacy attendants, the lower- level staff who stock and dispense drugs, allowing the technician more time for stock management and other more complicated tasks (Shulman et al. Because of task shifting, pharmacy technicians monitor adherence to antiretroviral treatment in Zambia and tuberculosis treatment in urban Uganda (Bolton-Moore et al. Training and task shifting programs that recruit minimally educated shopkeepers are also promising. For example, Kilif, Kenya, is a rural area of 70,000 people with 15 licensed dispensaries and pharmacies and 316 general stores that sell medicine (Marsh et al. A training program for Kilif shopkeepers more than doubled the proportion of antimalarials sold in adequate dosage (Marsh et al. A similar Kenyan program trained mobile wholesalers or wholesaler counter attendants to teach drug retailers about correct malaria drug dosing (Tavrow and Shabahang, 2002). After 6 months, mystery shoppers were nine times more likely to receive the correct drugs in the correct dose from retailers who had participated in the program (Tavrow and Shabahang, 2002). Giving Incentives to Pharmaceutical Personnel Using workers more effciently could do much to remedy chaotic drug retail in low- and middle-income countries, but there is also a problem of retaining trained staff in underserved posts. Even minimal technical train- ing confers a competitive advantage in the labor market, especially in poor countries (Attanasio et al. Newly minted pharmacy technicians or drug dispensers can easily leave their rural Copyright © National Academy of Sciences. This pattern can undermine the best efforts to improve rural-urban equity and should be discouraged, while respecting the individual right to emigrate. Governments should reward service in underserved areas and attempt to mitigate the hardships of these posts. Scholarships for the children of pharmacy staff in underserved areas could assuage fears that a rural posting puts their children at a disadvantage. Efforts to guarantee good schooling for children, possibly through boarding schools or scholarships, could remove a barrier to rural service (Rao et al. Health workers also have concerns about quality of life and physical hardships in rural posts (Rao et al. Subsidized housing or provi- sion of modern living quarters could help in places where this is a common concern. It is also possible to recruit pharmacy technicians and pharmacy assistants from underserved communities. Training students from rural and remote areas is a known way to reduce attrition in these posts (Rabinowitz et al. The Australian Rural and Remote Pharmacy program has successfully increased service to rural and isolated communities, in part through giving scholarships to students from rural backgrounds (see Box 5-4). Internet Pharmacies in Middle- and High-Income Countries Disorganized medicines retail is not confned to developing countries. The previous section describes the large gray market for medicines in ba- zaars and unlicensed drug shops in low- and middle-income countries. The internet serves the same purpose, but mostly in middle- and high-income countries. Illegitimate internet pharmacies are similar to unlicensed drug shops both in the quality of the products they stock, which is poor, and in the lack of offcial oversight of their operations (Crawford, 2003). And, because the internet facilitates easy international sales, online drug stores have spread the problem of falsifed and substandard drugs “from small, unproftable, markets in developing nations to the [drug] industry’s most lucrative markets” (Lybecker, 2007, p. The program aims to improve access to pharmacy services in rural or remote regions and includes a variety of initiatives to improve recruitment and retention of rural pharmacists. The program also increases pharmacy students’ exposure to rural work during their training. Australian pharmacy students work in com- munity or hospital pharmacies as part of their studies. The program also supports students from rural backgrounds to pursue pharmacy degrees. Another successful initiative to improve retention is the program’s emer- gency locum service. Figure 5-6 shows the geographic breakdown of the 30 countries that have legislation on the operation of internet pharmacies. A few countries have an accreditation process for their own internet pharmacies, but internet commerce is transnational. Perhaps concern about the practicality of enforcing laws against internet drug sales prevents countries from passing them. It may also seem futile to ask internet drug sellers to observe the same stan- dards registered pharmacies do, such as requiring doctor’s prescription for controlled medicines, when “national rules banning the sale of drugs with- out a prescription can be easily overcome” (Levaggi et al. Just as often, restrictions and quality controls for online pharmacies are not, in fact, violated because many internet pharmacies operate out of countries that have no such restrictions. Although regulatory agencies can ask foreign governments to close online drug stores, it is diffcult to prevent them from reopening at a different address (Ivanitskaya et al. Because the products are sent through courier or postal services, customs and border offcers may also stop the imported drugs at the port of entry (Ivanitskaya et al. The Attraction of Internet Pharmacies Some of the more reputable-looking internet drug sellers keep up the pretense of having patients complete a health questionnaire before buying drugs, but many do not (Ivanitskaya et al. Bostwick and Lineberry proposed four main categories of customers at internet pharmacies: bargain hunters, the poor or elderly, the “life- style libertines” who prefer to self-prescribe, and drug addicts (Baert and De Spiegeleer, 2010; Bostwick and Lineberry, 2007). Of these groups, ad- dicts are the least likely to purchase prescription drugs online (Inciardi et al. Internet drug stores cater to people who like to buy drugs with- out, or even against, a physician’s advice (Levaggi et al. Table 5-3 shows other perceived advantages and disadvantages of online pharmacies. Other online shoppers seem motivated by a belief, sometimes a mis- taken one, that internet pharmacies sell cheaper drugs. On average, the investigators paid more for the drugs that never arrived than for those that arrived (€0.

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Thus in this case cyclization not only improved stability but led to oral activity that was not present in the parent linear conotoxin cheap simvastatin 10 mg online. A cyclic melittin analog exhibited increased antibacterial activity order cheap simvastatin on line, with reduced hemolytic propensity buy cheap simvastatin 10mg, whereas a cyclic magainin 2 derivative was not so successful and had reduced antibacterial activity and increased hemolytic propensity [294]. The proper design of bioactive cyclic peptides requires detailed knowledge of the role of each amino acid residue, so that for example, cyclization should be designed to not affect residues that are crucial for activity [278]. Another consideration is the selection of a correctly sized linker, which must span the distance between the N and C termini. The adverse effects of removing stabilizing charge-charge interactions between the termini have to be overcome with linkers of correct length [287]. Nevertheless, with due consideration of these potential caveats peptide cyclization is a widely applied technique in the pharmaceutical industry, which decreases proteolytic degradation, prolongs half-life and stability and can improve binding effciency [278]. They are very important for the folding and stability of proteins, and in peptides they introduce conformational con- straints that confer a bioactive and thermodynamically stable conformation [296]. Disulfde-rich peptides can be used as stable scaffolds to graft exogenous peptide epitopes onto their stable structure, giving them new, and desired properties. Such scaffolds include the cyclotides [202], the defensins [297, 298], and the conotoxins [299] already described in this article. Because of their various disulfde connectiv- ities and a wide range of activities, these natural peptides offer a large diversity of stable molecular scaffolds. To supplement this natural set of scaffolds, the engineering of new intramolecular disulfde bonds into peptide structures is a valuable strategy for the design of peptidic compounds with desired structural and active properties [300]. For example, nonnative disulfde bonds have been used to induce a constrained and stable structure in peptides, such as an amphipathic α-helix [301–303] or β-hairpin [279, 300]. Peptides with potential antimicrobial activity were shown to possess bet- ter membrane binding, and enhanced antimicrobial potency, when a nonnative bond was introduced [279, 303, 304]. The use of diselenide bonds in place of disulfde bonds has been a particularly popular approach as the surrogate is almost isosteric but is more resistant to reduction [306–308]. The potency and selectivity of these natural compounds, including peptides, has made them of interest in the feld of drug design. In some cases, natural peptides have already been approved and are used as drugs or as food preservatives, while many others are in the pipeline of pharmaceutical com- panies. In this review, some examples of peptides isolated from different organisms with potential as therapeutic compounds have been illustrated. Such applications are facilitated by chemical modifcations and peptide engineering to improve drug-like properties of peptides. Although only limited examples have been described, the future appears to be bright for applications of natural peptides as drug leads. The value of Nature’s natural product library for the discovery of New Chemical Entities: the discovery of ingenol mebutate. Combinatorial peptide libraries in drug design: lessons from venomous cone snails. Recent progress towards pharmaceutical applica- tions of disulfde-rich cyclic peptides. Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy. Chemical and genetic characterization of bacteriocins: antimi- crobial peptides for food safety. Capacity of human nisin- and pediocin-producing lactic acid bacteria to reduce intestinal colonization by vancomycin-resistant enterococci. Antibacterial activity evalua- tion of microcin J25 against diarrheagenic Escherichia coli. Biosynthesis and insecticidal prop- erties of plant cyclotides: the cyclic knotted proteins from Oldenlandia affnis. Cyclotides as grafting frameworks for protein engineering and drug design applications. Plant cyclotides: a unique family of cyclic and knotted proteins that defnes the cyclic cystine knot structural motif. Lindholm P, Goransson U, Johansson S, Claeson P, Gullbo J, Larsson R, Bohlin L, Backlund A. Host-defense peptides in skin secretions of African clawed frogs (Xenopodinae, Pipidae). Potential therapeutic applications of magainins and other antimicro- bial agents of animal origin. Lorin C, Saidi H, Belaid A, Zairi A, Baleux F, Hocini H, Belec L, Hani K, Tangy F. Antimicrobial peptides from amphibian skin potently inhibit human immun- odefciency virus infection and transfer of virus from dendritic cells to T cells. In vitro antiviral activity of dermaseptin S(4) and derivatives from amphibian skin against herpes simplex virus type 2. Ziconotide - a novel neuron-specifc calcium channel blocker for the intrathecal treatment of severe chronic pain - a short review. High-throughput generation of small antibacterial peptides with improved activity. Antimicrobial proteinaceous compounds obtained from bifdobacteria: from production to their application. Screening and characterization of surface-tethered cationic peptides for antimicrobial activity. Direct virus inactivation of tachyplesin I and its isopeptides from horseshoe crab hemocytes. Antimicrobial peptides: a natural alternative to chemical antibi- otics and a potential for applied biotechnology. Folding of amphipathic alpha-helices on membranes: energetics of helix formation by melittin. Thermodynamics of the alpha-helix-coil transition of amphipathic peptides in a membrane environment: impli- cations for the peptide-membrane binding equilibrium. Antimicrobial peptides isolated from skin secretions of the diploid frog, Xenopus tropicalis (Pipidae). Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. Antibacterial and haemolytic pep- tides containing D-alloisoleucine from the skin of Bombina variegata. Bombinin-like peptides with antimicrobial activity from skin secretions of the Asian toad, Bombina orientalis. Structure-function relationships in bombinins H, antimicrobial peptides from Bombina skin secretions.

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