The substitution of insects for laboratory animals in toxicity testing is likely to become a reality in the framework of prescreening. Haematotoxicological studies of newly developed chemicals, such as food components, drugs, etc. performed on insects can offer advantages in, for example, environmental toxicology. Reliable routine predictions should produce an increase in our knowledge of haemocyte physiology. Although the differences between human physiology and morphology and those of insects are great, the basic functions of insect haemocytes and mammalian leukocytes appear not to have changed during evolution. The use of insects in haematotoxicity assays represents a preclinical testing strategy which will lower costs, accelerate screening and offer ethical benefits.

• MeSH
• alternativy výzkumu na zvířatech * MeSH
• druhová specificita MeSH
• hmyz účinky léků   MeSH
• krevní buňky účinky léků   MeSH
• krevní nemoci chemicky indukované   MeSH
• prediktivní hodnota testů MeSH
• preklinické hodnocení léčiv metody   MeSH
• testy toxicity metody   MeSH
• xenobiotika toxicita   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• xenobiotika MeSH

An attempt to replace the "in vivo" testing by "in vitro" exposure of cells to drugs is discussed from the point of view of the limitations of these artificial test conditions. The critical reminders are evaluated, the most important ones being the pharmacokinetics, pharmacodynamics and metabolism of drugs in the body what may be a cause of the discrepancy between "in vivo" and "in vitro" exposure assays. Various sensitivity of different cell types and of different phases of the generation cycle represent the crucial importance in the immune response and in the drug-cell interactions. The "in vitro" assays are technically sophisticated and mostly based on the tissue-culture techniques. However, both in immunology and immunotoxicology standardization, validation and usage of rules of Good Laboratory Practice are required. Finally, possibilities and contribution of "in vitro" assays to immunotoxicology are listed. It is apparent that for establishment of common rules these studies require intensive international and interlaboratory cooperation and coordination.

• MeSH
• analýza nákladů a výnosů MeSH
• biotest ekonomika   metody   MeSH
• epidemiologické metody MeSH
• epidemiologické monitorování MeSH
• hodnocení léčiv ekonomika   metody   MeSH
• imunitní systém účinky léků   MeSH
• imunologická odpověď na dávku MeSH
• laboratoře organizace a řízení   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• monitorování životního prostředí MeSH
• preklinické hodnocení léčiv ekonomika   metody   MeSH
• řízení kvality MeSH
• senzitivita a specificita MeSH
• toxikologie ekonomika   metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Hyaluronan (HYA) is a high molecular weight glucosaminoglycan with a great perspective for medical applications. Because HYA is widespread in the body, it is difficult to determine the fate of exogenously administered HYA. METHODS: In this study, HYAof different molecular weights (0.1-1 MDa) was labelled with (99m)Tc, and the distribution profiles were determined after administrating the HYA to rats. RESULTS: After the intravenous administration of (99m)Tc-HYA, a rapid decrease in the radioactivity of blood samples was observed, presumably because of (99m)Tc-HYA uptake by the liver; only minimal signs of liver radioactivity washout were detected. After the oral administration of (99m)Tc-HYA, no significant absorption to the central compartment was found. A preliminary study using (14)C-HYA exhibited a different distribution profile than (99m)Tc-HYA because of the different administered dose and the fate of the degradation products. Even with (14)C-HYA, only traces of radioactivity were absorbed after oral administration. CONCLUSION: This paper provides quantitative information regarding the distribution parameters of radiolabelled HYA in preclinical experiments.

• MeSH
• 99mTc-technecistan sodný MeSH
• aplikace orální MeSH
• gastrointestinální trakt metabolismus   MeSH
• gelová chromatografie MeSH
• injekce intravenózní MeSH
• játra metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyselina hyaluronová krev   chemie   farmakokinetika   MeSH
• ledviny metabolismus   MeSH
• molekulová hmotnost MeSH
• orgánová specificita MeSH
• potkani Wistar MeSH
• preklinické hodnocení léčiv MeSH
• radiofarmaka MeSH
• radioizotopy uhlíku MeSH
• stabilita léku MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 99mTc-technecistan sodný MeSH
• kyselina hyaluronová MeSH
• radiofarmaka MeSH
• radioizotopy uhlíku MeSH

BACKGROUND: Radiolabelled monoclonal antibodies with affinity towards tumour-associated antigens may enhance the efficacy of cancer treatment with targeted radiotherapy. The humanized antibody nimotuzumab represents a promising vector to deliver radioactivity to tumours overexpressing epidermal growth factor receptor type 1 (ErbB1). We analysed the effect of radiolabelling nimotuzumab on its uptake in cancer cells and its biodistribution profile in preclinical experiments. METHODS: Nimotuzumab was labelled with (131) I by oxidative iodination and with (177) Lu using nimotuzumab conjugates with two different chelators (DTPA and DOTA) and two different spacers (p-SCN-Bn and NHS). For the receptor studies, two cell lines (HaCaT and A431) were used. Biodistribution studies were performed in male Wistar rats. RESULTS: The choice of radiolabel and the manner of its attachment to nimotuzumab had little effect on the internalization of the antibody into ErbB1-expressing cell lines. However, the type of radiolabel, the way in which it was attached to nimotuzumab and the radiolabelling procedure, significantly affected the blood clearance, liver uptake and liver persistence of radiolabelled nimotuzumab. (131) I-nimotuzumab had the longest elimination half-life and the lowest radioactivity uptake in the liver. (177) Lu-labelled nimotuzumab exhibited a shorter elimination half-life, high radioactivity and long-term retention in the liver.

• Klíčová slova
• 131I, 177Lu, EGFR, nimotuzumab, preclinical biodistribution, radiopharmaceutical,
• MeSH
• humanizované monoklonální protilátky chemie   farmakokinetika   farmakologie   MeSH
• izotopové značení MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• lutecium chemie   farmakokinetika   MeSH
• nádorové buněčné linie MeSH
• preklinické hodnocení léčiv MeSH
• radiofarmaka chemická syntéza   farmakokinetika   farmakologie   MeSH
• radioizotopy jodu chemie   farmakokinetika   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• humanizované monoklonální protilátky MeSH
• lutecium MeSH
• nimotuzumab MeSH Prohlížeč
• radiofarmaka MeSH
• radioizotopy jodu MeSH

CONTEXT: Bryostatins represent an important group of pharmaceutically promising substances. These compounds are produced by commensal microorganisms naturally occurring in marine invertebrates, mainly in bryozoans. The most frequently investigated substance is bryostatin-1, which is a highly oxygenated macrolide with a polyacetate backbone. OBJECTIVE: The aim of this work was to summarize documented preclinical and clinical effects of bryostatin-class compounds. METHODS: A literature search was made of Medline and Web of Science databases in 2012. RESULTS AND CONCLUSION: Our review showed that bryostatins are potent agonists of protein kinase C. In addition to this, their significant antineoplastic activity against several tumor types has also been established and described. Bryostatin's anticancer activity has been proved against various cancer types. Moreover, significant results have been achieved by using bryostatin-1 in combination with other therapies, including combination with vaccine testing. Concerning other important properties that bryostatins possess, their ability to sensitize some resistant cells to chemotherapy agents, or immunoactivity and further stimulating growth of new neural connections, and enhancing effect on long-term memory are worth mentioning. In particular, some new bryostatin analogs could represent potential therapeutic agent for the treatment of cancer and other diseases in future.

• MeSH
• bezobratlí metabolismus   MeSH
• biologické přípravky chemie   farmakologie   MeSH
• bryostatiny chemie   farmakologie   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• nádory farmakoterapie   patologie   MeSH
• preklinické hodnocení léčiv MeSH
• proteinkinasa C účinky léků   metabolismus   MeSH
• protinádorové látky chemie   farmakologie   MeSH
• vodní organismy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické přípravky MeSH
• bryostatiny MeSH
• proteinkinasa C MeSH
• protinádorové látky MeSH

Based on the World Health Organization statistics, cardiovascular diseases represent the major cause of death worldwide. Although a wide range of treatment approaches and pharmaceuticals is available, the therapy is often not effective enough and therefore health risks for the patient persist. Thus, it is still essential to test new drug candidates for the treatment of various pathophysiological conditions related to cardiovascular system. In vivo models represent indispensable part of preclinical testing of such substances. Anesthetized guinea pig as a whole-body model allows to evaluate complex reactions of cardiovascular system to tested substance. Moreover, action potential of guinea pig cardiomyocyte is quite comparable to that of human. Hence, the results from this model are then quite well translatable to clinical medicine. Aim of this paper was to summarize the methodology of this model, including its advantages and/or limitations and risks, based on the effects of two substances with adrenergic activity on the ECG parameters. The model of anesthetized guinea pig proved to be valuable and suitable for testing of drugs with cardiovascular effects.

• MeSH
• elektrokardiografie * MeSH
• kardiovaskulární systém * účinky léků   MeSH
• kontrakce myokardu * účinky léků   fyziologie   MeSH
• krevní tlak účinky léků   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• morčata MeSH
• preklinické hodnocení léčiv * MeSH
• srdce účinky léků   fyziologie   MeSH
• srdeční frekvence MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• morčata MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The presented multistep program for testing immunomodulatory properties of biological response modifiers offers the possibility to evaluate multilaterally the modulatory potential of the tested preparations and to obtain basic data concerning their acute immunotoxicity. The scheme is divided into four stages: screening, optimalization, modelling, and analytical stage, each of which can be carried out separately on a relatively individual basis. This division considers the effect of the preparation on basic functions of the cells participating in the network of immunoregulation, the influence on the course of the immune response, modulation of the reactivity of the immune system affected by a 'non-immunological' phenomenon, as well as changes in protein repertoire produced by different systems of cells exposed to the tested preparation and/or the immunogenic signal. Detailed toxicological evaluation should be performed separately from immunopharmacological evaluation, keeping in mind differences in the application of the substances and the animal model involved. Incorporation of mathematical modelling and computer analysis of the results obtained by using the scheme may prove valuable in solving problems associated with potential modulation of the host immune system in clinically significant situations.

• MeSH
• adjuvancia imunologická * farmakologie   MeSH
• hodnocení léčiv metody   MeSH
• imunita MeSH
• lidé MeSH
• preklinické hodnocení léčiv metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adjuvancia imunologická * MeSH

• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   MeSH
• adjuvancia imunologická normy   terapeutické užití   toxicita   MeSH
• amantadin analogy a deriváty   farmakologie   MeSH
• dipeptidy farmakologie   MeSH
• imunologická odpověď na dávku MeSH
• imunoterapie MeSH
• myši MeSH
• prediktivní hodnota testů MeSH
• preklinické hodnocení léčiv metody   normy   MeSH
• reakce štěpu proti hostiteli účinky léků   MeSH
• replikace DNA účinky léků   MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• thymidinkináza antagonisté a inhibitory   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zánět chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• adamantylamide-alanyl-isoglutamine MeSH Prohlížeč
• adjuvancia imunologická MeSH
• amantadin MeSH
• dipeptidy MeSH
• thymidinkináza MeSH

As the world population ages, there will be an increasing need for effective therapies for aging-associated neurodegenerative disorders, which remain untreatable. Dementia due to Alzheimer's disease (AD) is one of the leading neurological diseases in the aging population. Current therapeutic approaches to treat this disorder are solely symptomatic, making the need for new molecular entities acting on the causes of the disease extremely urgent. One of the potential solutions is to use compounds that are already in the market. The structures have known pharmacokinetics, pharmacodynamics, toxicity profiles, and patient data available in several countries. Several drugs have been used successfully to treat diseases different from their original purposes, such as autoimmunity and peripheral inflammation. Herein, we divulge the repurposing of drugs in the area of neurodegenerative diseases, focusing on the therapeutic potential of antineoplastics to treat dementia due to AD and dementia. We briefly touch upon the shared pathological mechanism between AD and cancer and drug repurposing strategies, with a focus on artificial intelligence. Next, we bring out the current status of research on the development of drugs, provide supporting evidence from retrospective, clinical, and preclinical studies on antineoplastic use, and bring in new areas, such as repurposing drugs for the prion-like spreading of pathologies in treating AD.

• Klíčová slova
• Alzheimer's disease, aging, antineoplastic, dementia, drug repurposing, neurodegenerative diseases,
• MeSH
• Alzheimerova nemoc * farmakoterapie   MeSH
• demence * farmakoterapie   MeSH
• lidé MeSH
• pozorovací studie jako téma MeSH
• přehodnocení terapeutických indikací léčivého přípravku * MeSH
• preklinické hodnocení léčiv MeSH
• protinádorové látky * farmakologie   terapeutické užití   chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• protinádorové látky * MeSH

• MeSH
• imunita účinky léků   MeSH
• nežádoucí účinky léčiv * MeSH
• preklinické hodnocení léčiv metody   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH