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A precondition for the use of the very powerful „Suisepsin“ was that the strain of bacteria be known because it had to correspond to the serum buy 2.5 mg oxybutynin fast delivery medicine quetiapine. A less effective polyvalent serum was useful if the strain of bacteria was not known or the strain did not correspond to a known monovalent serum 2.5mg oxybutynin amex medicine used to induce labor, see Otto discount oxybutynin 2.5 mg overnight delivery medications zopiclone, Staatliche Prüfung der Heilsera, p. The serum control of polyvalent sera was much more complicated (and expensive) because the serum was tested on all the denoted strains of bacteria. Hüntelmann in a logical order, the next array under exactly the same conditions produced different results. Evaluation and standardization of Red Murrain Serum – Diffculties At frst, red murrain serum was evaluated like diphtheria serum: a constant quantity of bacteria bouillon (0,01 ccl) mixed with diminishing quantities of serum was injected into an array of mice. As a control animal, a mouse without any serum measured the virulence of the bacteria culture. Despite the reliability of this method of evaluation, irregularity appeared depending on the individuality of the mice and the duration of absorption of the serum within different mouse organisms (amboceptors and complements). The animal-based evaluation method was transformed into a primal-serum based model. As mentioned above, diminishing doses of the serum sample were injected into the mice and one hour later the bacteria culture was added. The injections were intraperitoneal to exclude proliferation that could infuence the effect and the evaluation. Next to a second array of non-immunized control mice a third array of mice was injected with a „standard serum“ – a vacuum-dried serum with a fxed value of one hundred immunisation units in one centilitre. To exclude any individuality or coincidences, every dose was injected into two mice resp. After an injection of serum and toxin the mouse should not have shown symptoms (L0-doses). The array ended with a minimum or lethal dose (L†) of serum, when the test mouse died within a specifed period. The test results between the standard serum and the serum sample had to be correlated. At times, the income and proft exceeded the proft derived from diphtheria serum (1905/1906: 6. It offered only a sheep based serum (without bacteria cultures), instead of a sheep-horse- cattle mixed serum that was complemented with anthrax bacteria cultures, the abovementioned „Simultanimpfung“. On the competition, see the correspondence in the Merck company archive in Darmstadt, K 1/128; on the theoretical issues, see the different articles of Sobernheim. Until then Ruete & Enoch mixed the tenfold doses of serum and bacteria cultures while establishing the value and the impact of bacteria culture was not proportional to the impact of the serum. For instance, to exclude uncertainty in the test procedure, the Ludwig Wilhelm Gans laboratory asked in September 1910, if a batch could be tested „privatim“ before the regular test procedure started, because they want to make sure that the serum batch passed the test 73 Axel C. As well as a vacuum-dried „standard-serum“, a standard- culture was also sent to the companies. Tested in the institute, the evaluation was fxed far below the announced value and the company had to explain itself to the Ministry of Cultural Affairs. Nevertheless, the “under-valued” serum had to be taken off the market and the difference was never explained. The precise procedures of evaluating the impact of red murrain or other sera on the immunized animal, expressed in numerical immunisation units derived from an animal experiment in the laboratory, was standardized. Conficts that arose were clarifed with the help of the institute and on its terms. Not only the serum and its therapeutic value, but also the process of evaluation itself became increasingly standardised. At the end of every test procedure, the institute fxed the value – independent of the practical effectiveness of the serum. Individual or local factors were excluded or, perhaps better put, simply declared non- existent. The complex procedure of evaluation worked as a technology of trust35 because the practical impact was independent of the value fxed by the institute, as the example of anthrax showed. Anthrax serum could not offcially be evaluated, but the serum was practically effective. Offcially tested serum was treated like a trademark and seen to be of better or „guaranteed“ quality. In the frst years serum producers offered compensation for any pig that died after or despite a preventive immunisation of serum production in order to strengthen confdence in red murrain serum and its use. After several years, once the method and value of immunisation against red murrain was „undoubtedly clear“, „safe“ and the „impeccable quality“ of the state-approved serum guaranteed, compensation was cancelled. The original aim of the state’s regulation of a biological drug was to minimize public health risk or similar biopolitical dangers. In addition, different aims from various actors became relevant: stabilizing and standardizing the production process, minimizing legal risks that could result from a patient’s death after an injection with diphtheria serum, or – for veterinary sera – the outsourcing of an economic risk. Hüntelmann 76 French and German Diphtheria Serum Research and the Reconfguration of Cultural Boundaries French and German Diphtheria Serum Research and the Reconfguration of Cultural Boundaries1 Ulrike Klöppel At the seventh International Congress of Hygiene and Demography in London in August 1891 two ambitious doctors met each other for the frst time: Emil Behring (1854-1917), an assistant of Robert Koch at the newly founded Institute for Infectious Diseases in Berlin, and Émile Roux (1853-1933), head of the department for technical microbe research at the Pasteur Institute in Paris. In the years that followed, both would become key protagonists in the experimental production of the diphtheria serum, which ultimately led to the mass production of serum for human use starting in 1894. Their lectures at the London congress were both concerned with the fndings that Behring had published in the winter of 1890: together with Shibasaburo Kitasato (1852-1931) he had demonstrated that blood serum from guinea pigs immunized against tetanus could be used to immunize and even to cure other animals. In Roux’s view, immunity was induced primarily by „phagocytosis“, that is to say as part of the „struggle between microbes and cells“. Emil Behring and Shibasaburo Kitasato, „Ueber das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren. Emil Behring, „Untersuchungen über das Zustandekommen der Diphtherie-Immunität bei Thieren. Roux repeated his objections in the discussion following Behring’s lecture at the London congress: Émile Roux, «Discussion. Thus, in front of the international audience he proclaimed: „Like the vital force in earlier times, so today the mysterious forces of the vital cell play a paralyzing role in our theories of immunity”.

This means that not every person will themselves carry the gene or become drug dependent generic 5 mg oxybutynin visa treatment 6 month old cough. Evidence for the heritability of drug use is derived from a range of research designs 5mg oxybutynin fast delivery medications information. The most robust evidence for the genetic influence of drug use comes from twin studies; research using family- and adoption-based designs has also shown an effect buy oxybutynin 5mg treatment math definition. Given the breadth of high-quality research using twin studies, this section will only briefly examine family- and adoption-based designs, before focusing on twin studies. While there is evidence that substance use disorders cluster in families, it is not clear from family-based designs whether these can be wholly attributable to heritable factors. This is because the family design cannot distinguish between whether the cause of familial similarity is genetic or environmental in nature. Adoption studies are based on a comparison of the concordanceb between offspring behaviour and the characteristics of both the adoptive and biological parents. Similarity between offspring and biological parents is suggestive of genetic influences, although research studies in this area should correct for in utero exposure to drugs. Adoption studies have reported a strong link between biological parents’ substance use, and their offsprings’ risk of addiction. A 1995 analysis of adoptees with substance- dependent biological parents (parents that were alcohol and/or drug dependent) compared with controls (adoptees with non-substance-dependent biological parents) provided an early demonstration of the role of genetic factors in the development of drug use and dependence. As genotypes and family environments tend to be similar, twin studies provide greater clarity in disentangling the role of genetic and environmental influences on drug use. Research using twin studies has reported a large degree of heritabilityc in relation to drug use. A 2006 review of the genetic epidemiology of cannabis use, abuse and dependence found evidence that there is a genetic basis to each of these three stages. Despite this, genetic factors are not exclusively responsible for the development of drug use and dependence. As is detailed in the following sections, there are a wide range of other factors that may influence drug use. Individual differences in behaviour may be due to genetic or environmental factors, and/or random chance. In recent years, a considerable amount of research literature has documented associations between drug use and dependence, and a range of psychiatric disorders. This is because of the difficulty in separating out true underlying disorders from behaviours that develop as part of drug use. Available clinical, neurobiological and epidemiological evidence is yet to identify a unified explanation as to why there is such a high concordance between drug use and mental illness. It is assumed that the presence of an initial psychiatric illness may, either directly or indirectly, increase the risk of drug use. One of the most widely cited explanations of this causal relationship between psychiatric illness and drug use is that drugs are used to self-medicate the negative pervasive symptoms of psychiatric illness. This is both because the evidence from these investigations is considered relatively weak in determining causality, and because they are limited in number. Drugs alter the normal functioning of brain mechanisms that exist to regulate the functions of mood, thoughts and motivations. A component of why individuals may wish to use drugs is to elicit an alteration in normal brain function. This may include the desire to experience pleasure or to avoid pain (the desired effects of commonly used illicit drugs are explored in greater detail in Appendix 2). Thus, at a biological level, both the immediate and long-term reasons for why people may use a drug can be rationalised by understanding how that drug affects the brain at the pharmacological level. The repeated use of drugs may contribute to their continued re-administration through the development of physical symptoms. These include: • tolerance: which can be defined as a given drug producing a decreasing effect with repeated dosing. Tolerance influences repeated drug use, and as a result larger drug doses must be administered to produce a similar effect • withdrawal: which is the body’s reaction to absolute or relative withdrawal of a drug. Withdrawal is associated with a range of significant negative physical and psychological outcomes, and in certain cases can be fatal. Withdrawal can be alleviated by readministering the drug, which contributes to its repeated use. Among those with sensation seeking as a personality trait, under-responsiveness to natural rewards and the need for greater stimulation has been suggested as motivation for drug taking. Personality traits have been documented to have a substantial heritable component. These models seek to explain addictive behaviour as pairings between a drug, drug-associated stimuli,e and the effect of taking a drug. Enduring changes to behaviour result from, or are influenced by, these interactions. Learning theory may be useful to understand how drug use becomes a facet of identity, and the implications this may have on treatment. In these instances, specific maladaptive traits may become reinforced over time, through the acquisition of drugs or perceived protection against negative experiences (see Chapter 8 for further information on the ‘addict identity’). The rewarding properties of drugs can include sensations of pleasure or relief of pain, tension or fatigue, as well as the ability to enable the user to escape negative feelings or emotions. Thus, the drug is used, it has rewarding effects, and this reinforces repeating this behaviour (ie it influences the continued use of the drugs). The use of psychoactive drugs causes activation to areas of the brain that are normally involved in motivation, such as the mesolimbic dopamine system (see Section 1. This causes the release of dopamine, the neurotransmitter released in response to any positive event or reward. Theories based on classical conditioning are often used to explain complex behaviours, such as drug craving. Research has demonstrated that after repeated drug administration, cues that precede drug ingestion, such as the sight of a needle and syringe, elicit craving for drugs.

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Nowadays almost everyone has some irrational fear discount 2.5 mg oxybutynin with visa treatment lichen sclerosis, for example cheap oxybutynin 2.5 mg without a prescription medicine clipart, regular medical examination buy discount oxybutynin 2.5mg symptoms yellow eyes. In this research, I identified several goals: to learn the genetic and environment causes of the occurrences of phobias; to determine the major types of phobias; to understand their influence on the body; to identify the methods of treatment. There are three main reasons that play a significant role in causing anxiety and phobic disorders: genetic factors, social factors, and psychological factors. According to scientists, a connecting link between the presence of phobias and accelerated aging are the telomeres. Scientists suggest that a lot of stress accelerates shortening of chromosome fragments. A shortened telomeres increase the risk of cancer, heart disease and neurodegenerative diseases. There are two main methods for the treatment of phobias: medical treatment and analytical treatment. Fear is an ordinary protective function, without which it will never work for self-preservation instinct, and this, in turn, can be a reason of tragic consequences. The fear can provide the biological survival of the individual and at the same take pathological forms. In this case, the intervention of the psychologist or psychotherapist is necessary. Scientists should pay more attention to the field of the phobias, their influence on the human body and more effective methods of treatment. In every age it has its own characteristics and susceptibility to certain problems. As you know, the skin is an important organ of cover, so-called protective barrier for the whole body. Among the internal factors that influence the skin condition is heredity, metabolic disorders and various diseases of internal organs. Different methods are highly effective, but are expensive and require a lot of time. To develop and recommend an easy, effective and popular way to prevent skin aging. To achieve this goal we worked out the literature and found that most meet the requirements rejuvenating facials masks, which are used in home conditions. The principle of action of the rejuvenating masks is that when in contact with skin mask substances moisturize and nourish it, improve microcirculation and, consequently, color, stimulate the regeneration of skin cells. For the experiment, we chose those ingredients that are easily available to all citizens. The recipe was as follows: milled oatmeal mixed with orange juice and a teaspoon of honey. After the study, all the women were satisfied with the result: improved skin color, decreased or disappeared excessive dryness and flaking, wrinkles became less noticeable, improved overall health, mood. Negative effects, side effects and complications any women were noted, which allows us to use the proposed mask for widespread use. Thus, carrying out the study, we have proved that rejuvenating masks at home are really effective, activate skin rejuvenation processes, inhibit the aging process. Another important advantage of their use is the naturalness, safety and financial affordability. Corn oil is attracting the attention of quite a high content of fat-soluble vitamins A and E and a favorable ratio of their different forms. On the other hand, quantitatively predominant component of the fatty acid composition of corn oil is diene linoleic acid which acts as though vitamin F, but is prone to peroxidation series to form intermediate products with extremely undesirable physiological effects. Therefore, among the areas of improvement of maize for special attention to the quality of oil particularly noteworthy increase in the content monoenic oleic acid, which has high thermal stability and significantly increased resistance to peroxidation. And, despite the significant amount of the research, reliable sources of high oleate content in maize has not yet been identified. Genetic analysis of oleic acid glycerides content in corn lines and hybrids oil and genetic identification of corn oil sources with a high content of oleic acid for pharmaceutical practice using. The material for the research were presented as a representative samples of kindred origin of the traditional type of maize lines and lines-carrier of endospermic monogenic mutations reliably registered beneficial effect on the seed biochemical composition - o2 (opaque-2), sh1 (shrunken-1), sh2 (shrunken-2) , su1 (sugary-1), su2 (sugary-2), ae (amylose extender) and wx (waxy). Genetic analysis was performed on a series of hybrids which were obtained by cross of lines with identical allelic status of each of the genes in the endosperm structure schemes diallel crosses by Griffings method. The fatty acid composition of the oil was analyzed by modified Peysker gas chromatographic method after transesterification of glycerol esters into methyl one. Identification of fatty acid component composition was carried out at the time of their retention, set to valid standards. The results showed endospermic mutants high efficiency to improve oil fraction of oleic acid glycerids. However, these results cannot be considered as evidence of the content of the monogenic regulation of recessive oleate mutant genes su1 and sh2 yet. As in the usual corn, as in carriers of mutations of the above oleate content was clearly a quantitative nature and varied rather widely. At the same time the best lines of the traditional type of maize reached levels of oleate 34. The results showed that even if the monogenic regulation of oleate content by third and fourth chromosomes locuses occurs, it is carried out not by su1 and sh2 genes, but by the linked space with them oleate coding locuses. On the other hand, the results indicate that the effects of monogenic locuses are modified by polygenic complexes that can both strengthen and weaken the level of phenotypic feature manifestation. When the genetic trait analysis was conducted it was found that high level of oleate regulated by polygenic type and system of genetic regulation of oleate content approaches to the additive - dominant Hayman model. The predominant type of high oleate content inheritance was incomplete dominance with a significant contribution to the dispersion of the additive effects. Such type of inheritance creates favorable conditions for the improvement of the genetic trait. At the same time inbreed lines of maize, based on a single mutation, were very differed by the effects of combining ability according to the content of oleate. It has been established that high levels of oleate in corn oil is regulated by the combined effect of the third and fourth chromosomes locuses and modified by chromosomes polygenic complexes. The most promising genetic material for improving the content of oleate are the carriers of endospermic mutations su1 and sh2.

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The compound originally isolated from rotting fish meal and named vitamin K2 was later identified as menaquinone-7 (2-methyl-3-farnesylgeranyl-geranyl-1 5mg oxybutynin with amex symptoms 5 weeks pregnant,4-naphthoquinone) order oxybutynin 2.5 mg treatment efficacy. In the older literature buy 2.5 mg oxybutynin mastercard medications 563, the designation vitamin K2(35) is used for menaquinone-7, but this is no longer used. Menaquinones found in nature have side-chains of 4–13 isoprenoid residues and are usually in the all-trans configuration; however, menaquinones with the cis confi- guration and partially saturated side-chains also exist (Suttie, 1985, 1991; Weber & Rüttimann, 1996; Van Arnum, 1998). Phylloquinone occurs in nature only as the 2′,3′-trans-phylloquinone stereoisomer (Weber & Rüttimann, 1996; American Hospital Formulary Service, 1997; Council of Europe, 1997). Phylloquinone is available as a 5- and 10-mg tablet (chewable), a 2- and 10 mg/mL injection solution, a 10- and 20-mg/mL oral solution and a 20-mg/mL emulsion. The tablet may also contain carmellose, carob bean flour, carob gum, cocoa butter, cocoa powder, ethyl cellulose, ethyl vanillin, glucose, glycerol, gum arabic, hard and viscous paraffin, lactose, rice starch, sugar, silicic acid, silicon dioxide, skim- milk powder, sodium cyclamate, talc and titanium dioxide. The injection solution may also contain benzyl alcohol, dextrose, glacial acetic acid, glucose, glycocholic acid, hydrochloric acid, macrogol ricinoleate, phenol, phosphatidylcholine from soya beans, polyethoxylated fatty acid derivative (castor oil), polysorbate 80, propylene glycol, sodium acetate, sodium hydroxide and water. The oral solution may also contain benzoic acid, glycocholic acid, hydrochloric acid, lecithin, macrogol ricino- leate, methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, sodium hydroxide and water. Menaquinone-4 is available in Japan as 5- and 15-mg capsules and as a 2-mg/mL syrup. The syrup may also contain polyoxyethylene hydrogenated castor oil 60, propylene glycol, ethyl parahydroxybenzoate, sodium benzoate and flavouring (Japan Medical Products Trade Association, 1996). Trade names for menaquinone-4 include Glakay and Kaytwo (Japan Medical Products Trade Association, 1996). Menadione is available as a 2-, 5- and 10-mg tablet and as a 2- and 10-mg/mL injection (in oil). Menadione sodium bisulfite is available as a 10-mg tablet and as a 5- and 10-mg/mL and 72-mg/10 mL injection (Gennaro, 1985). Trade names for menadione sodium bisulfite include Austrovit-K, Golagen K, Hemoklot, Hetrogen K, Hetrogen K Premix, Hykinone, Ido-K, K-Thrombin, K- Trombina, Kalzon, Kareon, Kavitamin, Kavitan, Kavitol, Kawitan, Klotogen, Libavit K, Nuvit K, Vikaman, Vikasol, Vitaminum K and Zimema K (Swiss Pharmaceutical Society, 1999). Trade names for menadiol sodium phosphate hexahydrate include Kappadione, Kativ (injection), Kipca water soluble, Naphthidone, Procoagulo, Synkavit, Synka- Vit, Synkavite, Synkayvite and Thylokay (Swiss Pharmaceutical Society, 1999). Trade names for acetomenaphthone include Adaprin, Davitamon-K, Davitamon-K- oral, Kapathrom, Kapilin, Kapilon, Kappaxan, Kativ powder, Kayvite, Pafavit, Pro- kayvit Oral and Vitavel K. The limit of detection of phylloquinone is 25–500 pg, depending on the detection method used. Similar values, which vary according to the length of the side- chain, apply to the menaquinones. Alternative methods are thin-layer chromatography, high-performance thin-layer chromatography and gas chromatography. The stability of phylloquinone to heat made possible the use of commercially dehydrated alfalfa meal, for example, as a natural source (Hassan et al. The synthesis and spectral properties of all four stereoisomers of (E)-phylloquinone have been described and their biological potencies determined. When natural phylloquinone was used as a standard in bioassays, it was concluded that all four stereoisomers have essentially identical activity (Van Arnum, 1998). The first syntheses and structural elucidation of phylloquinone were published in 1939 almost simultaneously by four groups. The starting materials were menadione or menadiol as the aromatic component and natural phytol or one of its derivatives. A breakthrough in commercial synthesis was achieved in the 1950s, when it was found that monoacylated menadiols (e. In the Isler-Lindlar method, excess menadiol monobenzoate is condensed with iso- phytol in the presence of boron trifluoride etherate as a catalyst. The trans-enriched alkylation product (trans:cis 9:1) is saponified with potassium hydroxide and oxidized to phylloquinone with oxygen (Weber & Rüttimann, 1996). The industrial synthesis of menaquinones parallels that of phylloquinone and involves as a key step alkylation of monosubstituted menadione with an appropriate (all-trans) polyisoprenyl derivative. Menaquinones of varying chain lengths, from C5 to C65, have been produced and isolated from bacteria. Menadione can be prepared by oxidizing 2-methylnaphthalene with chromic acid or hydrogen peroxide (Weber & Rüttimann, 1996). A process based on biotechno- logical techniques has been reported in Japan (Van Arnum, 1998). Menadione sodium bisulfite can be prepared by reacting menadione with sodium bisulfite. The compound readily regenerates menadione on treatment with mild alkali and behaves as a typical ketone–sodium bisulfite addition compound (Gennaro, 1985; Van Arnum, 1998). Menadiol sodium phosphate can be prepared by reducing menadione to the diol, followed by double esterification with hydriodic acid, metathesis of the resulting 1,4- diiodo compound with silver phosphate and neutralization of the bis(dihydrogen phosphate) ester with sodium hydroxide (Gennaro, 1995). The modification is catalysed by a micro- somal enzyme called γ-glutamyl or vitamin K-dependent carboxylase, which is present in most tissues. The best-known vitamin K-dependent proteins are those synthesized in the liver, which play a role in the maintenance of normal haemostasis. Vitamin K-dependent proteins, of uncertain function, are also known to occur in a variety of other tissues such as bone, kidney, pancreas, placenta, spleen and lungs. They include the bone protein osteocalcin (also called bone Gla protein) and matrix Gla protein; there is growing evidence that these proteins may be important for bone health and other regulatory functions in calcium metabolism. Naturally occurring phylloquinone and menaquinones all γ-carboxylate the vitamin K-dependent coagulation proteins. Synthetic forms of menadione (and related water-soluble salts) that lack a side-chain at the 3-position have biological activity in vivo only after side-chain alkylation, which results in the specific synthesis of menaquinone-4 (Suttie, 1991; see also section 4). Neonates are born with very limited vitamin K stores, but most infants do not show relevant hypoprothrombinaemia at birth (von Kries et al. Biochemical signs of vitamin K deficiency are common during the first week of life, however, unless sufficient amounts of vitamin K are ingested. The natural diet of newborns is human milk, which contains vitamin K at concentrations of 0.