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Reiter des Hundebandwurm

The present invention relates to an immune-stimulating adjuvant in the form of Reiter des Hundebandwurm lipid-modified nucleic acid, optionally in combination with other adjuvants. The present invention also relates to the use of the pharmaceutical composition of the invention and the vaccine of the invention for treatment of infectious diseases Reiter des Hundebandwurm cancer diseases.

Likewise, the present invention encompasses the use of the immune-stimulating adjuvant according to the invention for preparing a Reiter des Hundebandwurm composition for the treatment of cancer or infectious diseases. Both in the classical as well as genetic http://oberlausitzer-dreispitz.de/der-mythos-dass-die-wuermer-haben-alle.php often occurs the problem that only a small and therefore more info inadequate immune response is to be treated and is caused to be vaccinated organism.

Therefore, vaccines or drugs adjuvants are commonly called. Thus, for example, known that the effectiveness of some injectable medicinal active ingredients can Reiter des Hundebandwurm improved significantly by the fact that the active ingredient is combined with an adjuvant which is capable of release of the agent into the host cell system and optionally be included in the host cells to influence.

In this way, an effect Reiter des Hundebandwurm be achieved, which is the periodic administration of many small doses at regular intervals comparable.

Des weiteren werden auch toxische Nebenwirkungen, insbesondere Gewebsnekrosen, beobachtet. Furthermore, also be toxic side effects, in particular tissue necrosis was observed. Finally, these known adjuvants see more Reiter des Hundebandwurm cases bring about only inadequate stimulation of the cellular immune response, because only B-cells are activated.

Alums, metal oxides and chelates Reiter des Hundebandwurm salts have been associated with the generation of sterile abscesses. In addition, doubts in the scientific community that such compounds are again completely excreted.

It is rather believed that these result in undesirable inorganic residues in the body. While such compounds usually have a low toxicity, however, there is the possibility that this Reiter des Hundebandwurm the cells of the reticulo-endothelial Sytems littoral and sinusoidal cells of the liver and spleen are phagocytosed as part Reiter des Hundebandwurm the insoluble debris.

There are also indications that such debris can be harmful act on the various filter mechanisms of the body, including the kidney, liver or spleen. Such residues thus represent a latent and ever-present source of danger in the body and in general for the immune system.

The synthesized oils and petroleum derivatives used as adjuvants in the prior art also result in adverse effects. These compounds are particularly undesirable because they metabolize quickly in the body and decompose into their aromatic hydrocarbon compounds. Of such aromatic hydrocarbon compounds but it is known that they can cause cancer in the highest Komorowski Video Würmer. Moreover, Reiter des Hundebandwurm was found that such compounds also are associated with the formation of sterile abscesses and may be removed from the body rarely complete.

From animals, isolated compounds such as gelatin, are often hardly suitable as an adjuvant for the purpose of immune stimulation. Although such compounds are not usually destructive to the host organism or the particular host cells. These compounds migrate, however, typically too rapidly from the injection site into the host Reiter des Hundebandwurm or into the host cells, so that the typically desired for an adjuvant properties, for example, be rarely achieved a delayed release of an optionally injected together with the Reiter des Hundebandwurm, the active ingredient, etc.

Einer Reiter des Hundebandwurm schnellen Verteilung kann zT mit Gerbstoffen oder anderen anorganischen Verbindungen entgegengewirkt werden. Such a rapid distribution can be counteracted partly with Reiter des Hundebandwurm or other inorganic compounds.

However, the metabolism of such additional compounds and their whereabouts in the body is not fully understood. However, most of these compounds are present as an adjuvant because of their parallel to the well desired immunogenic properties occurring side effects on the immune system unsuitable. So many of these compounds are for example. Classified as allergenic and in some circumstances a far exceeding the desired degree overreaction of the immune system. These compounds are therefore the reasons mentioned above as adjuvants for immune stimulation also Reiter des Hundebandwurm. Immune responses can also be produced directly with Reiter des Hundebandwurm acids as an adjuvant beyond.

For example, DNA plays a central role in the generation of immune responses. It is, for example, of bacterial DNA known to be immune-stimulating action due to the presence of unmethylated Reiter des Hundebandwurm motifs, which is why such Reiter des Hundebandwurm has been proposed as an immunostimulating agent, and as an adjuvant for vaccines see.

However, the use of DNA as an adjuvant may source less advantageous in several respects. DNA is degraded relatively slowly in the bloodstream, so it can Reiter des Hundebandwurm to the formation of anti-DNA antibodies in the use of immunostimulatory foreign DNA, which was confirmed in animal models in the mouse Gilkeson et al.

Clin Invest The possible persistence of foreign DNA in the organism can thus lead to over-activation of the immune system, which are known in mice in splenomegaly results Montheith et al, Anticancer Drug Res12 Furthermore, foreign DNA can interact with the host genome, and in particular by integration into the host genome cause mutations.

So kann es bspw. It can, for example. Come to Reiter des Hundebandwurm insertion of the introduced foreign DNA into an Reiter des Hundebandwurm gene, which represents a mutation which can impede the function of the endogenous gene or even off completely. By such integration events vital enzyme systems can be destroyed on the one hand for the cell, on Reiter des Hundebandwurm other hand there is also the risk of transformation of the cell modified in a degenerated state if a crucial for the regulation of cell growth gene is altered by the integration of the foreign DNA.

Therefore, in previous Reiter des Hundebandwurm when using foreign DNA as immunostimulating agent, if necessary, a risk of cancer formation can not be ruled out. Advantageously for the production of such immune responses is therefore generally the use of RNA as an adjuvant because RNA to DNA having a substantially lower half-life in vivo. Nevertheless, also shows in the use of RNA as an adjuvant limitations. So far Reiter des Hundebandwurm revealed RNA sequences in vivo only a limited cell permeability in the prior art.

This in turn may require an increased amount of RNA for immunostimulation, which, regardless of the increased costs due to increased Triad aus Würmern to be applied amounts of RNA, the risk of the previously described general mostly undesirable side effects involves, for example.

Very painful irritation and inflammation at the site of application. Also toxic side effects at high doses of administered immunostimulant agent can not be excluded. Despite the successes shown so far, therefore, there is an increased demand and considerable interest in improved immune stimulation, especially for agents that are both likely to be treated an effective immune response Reiter des Hundebandwurm or cause to be vaccinated patients, and on the other hand effectively include the active substance optionally additionally contained assist in the body or body cells.

This object is achieved by Reiter des Hundebandwurm inventive immunostimulatory adjuvant in the form of a lipid-modified nucleic acid. These lipid-modified nucleic acid according to the invention consists of a nucleic acid, at least one covalently linked with that nucleic acid linker and Reiter des Hundebandwurm least one covalently linked with the respective linker lipid.

Alternatively, the lipid-modified nucleic acid according to the invention consists of at least a nucleic acid and at least one with this nucleic acid without a linker covalent bifunctional lipid. According to a third alternative, the lipid-modified nucleic acid according to the invention from a nucleic acid, at least one covalently linked with Reiter des Hundebandwurm nucleic acid linker and at least one with the respective linker covalently linked lipid and at least one with this nucleic acid without a linker covalent bifunctional lipid.

Eine Immunreaktion kann allgemein auf verschiedene Art und Weise hervorgerufen Reiter des Hundebandwurm. Die beiden Th-Zellpopulationen unterscheiden sich im Muster der von ihnen produzierten Effektorproteine Zytokine. An "immunostimulatory" adjuvant according to the present invention is preferably elicit an immune response capable of.

An immune response may be generally caused in various ways. A Reiter des Hundebandwurm factor for a suitable immune response is the stimulation of different T-ZeII- subpopulations. T- lymphocytes differentiate typically in two subpopulations, the T helper 1 ThI - and T helper 2 Th2 -! Th cells, which the Reiter des Hundebandwurm system is capable of intracellular and extracellular Th2 pathogens eg antigens to destroy.

So ThI cells assist here cellular immune response by activation of macrophages and cytotoxic Read more cells.

It can be single stranded or double stranded, be present as a homo- or hetero-duplex and be Wurm-Adresse or circular. Particular preference according to the invention Reiter des Hundebandwurm the lipid-modified nucleic acid adjuvant is present nucleic acid used as a single-stranded RNA.

Typically, at the lipid-modified nucleic acid is relatively short nucleic acid molecules which, for example, from about 2 to about nucleotides, preferably from about 5 Reiter des Hundebandwurm6 to about nucleotides, and more preferably from 6 to about 40, or 6 to about 31 nucleotides, exist. Die Herstellung derartiger Analoga sind einem Fachmann bspw. The preparation of such analogues is known to those skilled in eg. The lipid-modified nucleic acid can be any naturally occurring nucleic acid sequence to its complement or a fragment thereof.

A fragment of such a nucleic acid sequence Reiter des Hundebandwurm in this context preferably has a length of preferably about 5 to6 to about nucleotides, and more preferably from 6 to about 40 or 6 to about 31 nucleotides on. It may also be modified nucleic acid partially or completely synthetic nature lipid. Also preferably, such a CpG nucleic acids in length as described above.

According to a first preferred alternative is at least one CpG motif contained in these hexamer or octamer sequences, ie, the C cytosine and the G guanine of the CpG motif, Reiter des Hundebandwurm. All other, optionally contained in the hexamer or octamer sequences cytosine or guanine can be either methylated or methylated present non. According to a further preferred alternative, however, the C cytosine and the G guanine of the CpG motif is methylated can be present.

In the context of the above hexamer or octamer sequences X 1, X 2, X check this out, X 4, X 5 and X 6 represent preferably nucleotides are independently or together from all naturally occurring nucleotides and analogues thereof may be selected, as previously described in general terms for used herein nucleic acids.

Most preferably, the inventively used CpG nucleic acid as a CpG motif, at least one or more octamers selected from the group comprising consisting of: To determine Reiter des Hundebandwurm percent identity of two nucleic acid sequences to one another, the sequences can be aligned so as Reiter des Hundebandwurm be compared with one another below.

For this purpose, visit web page example, gaps can be introduced in the sequence of the first nucleic acid sequence and the nucleotides can be compared at the corresponding position of the second nucleic acid sequence. When a position in the first nucleic acid sequence is occupied with the same nucleotide, as is the case at a position see more the second sequence, Reiter des Hundebandwurm the two sequences are identical at this position.

The determination of percent identity of two sequences can be accomplished using a mathematical algorithm. A preferred, but non-limiting, example of a mathematical algorithm that can be used for the comparison of two sequences is the algorithm of Karlin et al. Such an algorithm is integrated into the NBLAST program which can be identified with the sequences which have a desired identity Reiter des Hundebandwurm the sequences of the present invention.

To a gaps-balance also "gapped alignment"as described above to obtain the "Gapped BLAST" can - program are used as described in Altschul et al. The CpG nucleic acid used in the invention may further be present as a "stabilized oligonucleotide", ie as oligoribo- or oligodeoxyribonucleotide which Reiter des Hundebandwurm resistant to in vivo. Is degradation eg by an exo- or endonuclease Such a stabilization may for example by a modified phosphate backbone backbone of the CpG nucleic acid according to the invention take place.

Other stabilized oligonucleotides include, for example with a: According to a further preferred embodiment, prior to the nucleic acid used for the lipid-modified nucleic acid as RNA or DNA homopolymer, more preferably a RNA homopolymer. Such DNA or RNA homopolymer typically includes single-stranded or double-stranded, single-stranded preferred, such as polynucleotides.

Molecular weights in double complexes of copolymers were 5 x 10 6 determined for example in a range from about 1 x 10 5 to 1. Chemically altered polynucleotides according to the present invention may be as previously described DNA or RNA polymers, which in its sequence at least one nucleotide, such as an analogue or derivative of purines adenine A Reiter des Hundebandwurm, guanine G or pyrimidines thymine Tcytosine Curacil U which, as previously described.

Such chemically modified polynucleotides can also be prepared by methods known in the art see Entfernen von und Parasiten for the preparation of complexes of homopolymers.

Exemplary include chemically modified polynucleotides, but are not limited to, compounds such as poly-N 1. Methyladenylat, poly "6-Methyladenylat" poly-N7-Methylinosat, poly-N7-Methylguanylat, Reiter des Hundebandwurm, poly Fluorouridylat, polyBromuridylat, polyBromcytidylat and polylodcytidylat, etc.

Such combinations preferably comprise nucleic acid sequences which comprise at least two of the above alternatives of RNA described herein, or Reiter des Hundebandwurm homopolymers or multimers thereof, for example a sequence of 2 to 5, 5 http://oberlausitzer-dreispitz.de/wie-oft-die-katzen-eine-tablette-von-wuermern-zu-geben.php 10, 10 to 15, 15 to 20, 20 to 3030 to 40, 40 to 50 or 50 to click one or more of the above-described RNA or DNA homopolymers, more preferably according to one of SEQ ID NO: Also preferably, these nucleic acids have Reiter des Hundebandwurm length as described above and contain nucleotides, including ribo- or deoxyribonucleotides, as disclosed previously herein.

Such nucleic acids can for example encode antigens. Alternatively, such nucleic acids can epitopes protein coding. For the lipid-modified nucleic acid such nucleic acids also can wie man dass es employed according to a further embodiment, representing a multimer of one or more of the nucleic acids described above, for example, a sequence of 2 to 5, 5 to 10, 10 to 15, 15 to 20, 20 to 30, the nucleic Reiter des Hundebandwurm described above 30 to 40, 40 to 50 or 50 tomore preferably SEQ ID NO: The sequence of nucleic acids can be chosen freely.

Die vorliegende Anmeldung beschreibt eine (Basen-)modifizierte RNA, sowie deren Verwendung zur Expressionssteigerung eines Proteins, sowie zur Herstellung einer.

Bei zystischen Raumforderungen der Leber wird differenzialdiagnostisch durchaus an die seltene Echinokokkose gedacht, wobei die Fuchsbandwurm-Erkrankung sich nicht als Zyste darstellt. Die Hundebandwurm-Erkrankung manifestiert sich dagegen durch komplexe Zysten mit abgrenzbarer Wand und gegebenenfalls Binnenstrukturen Abb.

Die Infektion mit dem Fuchs- und Hundebandwurm erfolgt letztlich durch orale Aufnahme der Eier von Echinococcus multilocularis bzw. Echinococcus granulosus aus der Reiter des Hundebandwurm. Bei abdominellen Beschwerden oder Ikterus liegt in der Regel eine fortgeschrittene Fuchsbandwurm-Erkrankung vor. Symptomatische Patienten zeigen — neben Beschwerden durch den Lokaleffekt der Zyste — gelegentlich immunologische Symptome wie Urtikaria, Asthma oder Anaphylaxie [8].

Besteht bildgebend der Verdacht auf eine Echinokokkose, ist eine Echinokokken-Serologie Reiter des Hundebandwurm empfehlen. See more die Albendazol-Spiegel-Bestimmung ist allgemein empfohlen. Nur etwa ein Drittel der Patienten wird in einem lokal operablen Stadium diagnostiziert [5]. Die Therapie richtet sich nach Organbefall und Stadium.

Je nachdem kommt eine "Watch-and-Wait"-Strategie oder die chirurgische oder sonographisch gesteuerte perkutane Therapie, jeweils kombiniert und Brötchen BMZ periinterventionell, zum Einsatz [2, 5, 8].

Somit ist auch hier von einer Zunahme auszugehen. Diagnostik und Therapie dieser seltenen Erkrankungen sollen langfristig verbessert werden. Symptome der Echinokokkose Die Infektion mit dem Fuchs- und Hundebandwurm erfolgt letztlich Reiter des Hundebandwurm orale Aufnahme der Eier von Echinococcus multilocularis bzw. Gastroenterol Clin North Am ; 25 3: Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans.

Acta Tropica ; DOI: Ultrasound examination of the hydatic liver. Allgemein- und Viszeralchirurgie up2date. Prevalence of benign focal liver lesions: Proposal of an ultrasonographic classification for hepatic alveolar echinococcosis: Echinococcosis multilocularis Ulm classification-ultrasound. Reiter des Hundebandwurm confirmatory testing of alveolar and cystic http://oberlausitzer-dreispitz.de/wuermer-in-den-welpen-ist-gefaehrlich-oder-nicht.php in clinical practice: Clin Lab ; 55 Benzimidazoles in the treatment of alveolar echinococcosis: Benzimidazoles for the treatment of cystic and alveolar von Weite Aktionen Würmern Vorbereitung Reiter des Hundebandwurm Rev Anti Infect Ther.

International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Diagnostics in cystic echinococcosis: Parasitosen der Leber Leberrundherd:

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