Osteoartróza (OA) je chronické degenerativní onemocnění kloubů, které nejčastěji postihuje osoby starší 40 let. U pacientů může způsobit značná omezení hybnosti, bolest, diskomfort a celkové snížení kvality života. Jde o značně heterogenní onemocnění s komplexními patofyziologickými mechanismy a jeho příčiny nejsou zatím zcela jasné. Dosud se nepodařilo vytvořit takový animální model OA, který by postihoval všechny aspekty onemocnění u člověka. Z toho důvodu patří OA k patologickým stavům, pro něž bylo v minulosti definováno velké množství různých typů animálních modelů. V tomto přehledném článku je představena systematická klasifikace jednotlivých modelů a u nejpoužívanějších z nich jsou uvedeny jejich hlavní výhody a nevýhody. Za nedílnou součást většiny uvedených modelů lze považovat vznik, rozvoj, transmisi a percepci bolesti. Možnosti jejího hodnocení jsou proto důležitou kapitolou používání modelů OA. Text rovněž zmiňuje u několika modelů důležitost posouzení újmy pro pokusná zvířata. To dosud není u článků tohoto typu běžné.

Osteoarthritis (OA) is a chronic degenerative disease of joints. This disease most commonly affects people over the age of forty. It is a debilitating illness causing pain and immense discomfort to the affected individual. OA is a heterogenic disease with very complex pathophysiological mecha- nisms and the causes of OA are still unknown. There is currently no animal model of this disease that reflects all aspects of OA in man. Therefore, OA belongs to pathological conditions, for them many models of different types have been created. In this review article, the animal models are classified systematically, and their main advantages and disadvantages are listed for the most common ones. An important part of the described models is the onset, development, transmission and perception of pain and the possibilities of its measurement. The text also mentions the aspect of harm to the animals, which is not yet common in articles of this type.

• MeSH
• bolest chemicky indukované   chirurgie   patofyziologie   MeSH
• laboratorní zvířata MeSH
• modely nemocí na zvířatech MeSH
• modely u zvířat MeSH
• osteoartróza * klasifikace   patofyziologie   patologie   MeSH
• Publikační typ
• práce podpořená grantem MeSH

Poly(d,l-lactide)/polyethylene glycol (PLA/PEG) micro/nanofibers loaded with paclitaxel (PTX, 10 wt%) were prepared by needless electrospinning technology, which allows large scale production for real medicinal practice. The fiber structure and properties were investigated by several methods including scanning electron microscopy, nitrogen adsorption/desorption isotherm measurements, differential scanning calorimetry, and X-ray diffraction measurements to examine their morphology (fiber diameter distribution, specific surface area, and total pore volume), composition, drug-loading efficiency, and physical state. An HPLC-UV method was optimized and validated to quantify in vitro PTX release into PBS. The results showed that the addition of PEG into PLA fibers promoted the release of higher amounts of hydrophobic PTX over prolonged time periods compared to fibers without PEG. An in vitro cell assay demonstrated the biocompatibility of PLA/PEG fibrous materials and showed significant cytotoxicity of PTX-loaded PLA/PEG fibers against a human fibrosarcoma HT1080 cell line. The chick chorioallantoic membrane assay proved that PTX-loaded fibers exhibited antiangiogenic activity, with a pronounced effect in the case of the PEG-containing fibers. In vivo evaluation of PTX-loaded PLA/PEG fibers in a human fibrosarcoma recurrence model showed statistically significant inhibition in tumor incidence and growth after primary tumor resection compared to other treatment groups.

• MeSH
• buněčná smrt účinky léků   MeSH
• difrakce rentgenového záření MeSH
• inhibitory angiogeneze farmakologie   MeSH
• kur domácí MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   prevence a kontrola   MeSH
• myši nahé MeSH
• nádorové buněčné linie MeSH
• nanovlákna chemie   ultrastruktura   MeSH
• nosiče léků chemie   MeSH
• paclitaxel farmakologie   MeSH
• polyestery chemie   MeSH
• polyethylenglykoly chemie   MeSH
• tělesná hmotnost MeSH
• teplota MeSH
• tumor burden účinky léků   MeSH
• uvolňování léčiv * MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Baclofen is the only clinically available metabotropic GABA(B) receptor agonist. In our experiment, we tested the hypothesis that long-term baclofen administration can impair learning and memory in rats. The experiment consisted of three parts. In the first part of the study the drug was administered simultaneously with the beginning of the behavioral tests. In the second and third part of the experiment baclofen was administered daily for 14 days and for one month before the tests. In each part of the experiment, adult rats were randomly divided into four treatment groups. Three groups were given an injection of baclofen at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, while the fourth group was injected with saline. The injections were given after each session. Spatial learning and memory were tested using the Morris water maze, involving three types of tests: Acquisition, Probe, and Re-acquisition. This work reveals that baclofen did not affect spatial learning at any of the tested doses and regardless of the length of administration. Memory was observed to be affected, but only at the highest dose of baclofen and only temporarily. This conclusion is in line with previously published clinical cases.

• MeSH
• agonisté receptorů GABA-B aplikace a dávkování   MeSH
• baklofen aplikace a dávkování   MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• paměť účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• prostorové učení účinky léků   fyziologie   MeSH
• rozvrh dávkování léků MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Glutamate carboxypeptidase II (GCPII), also known as prostate-specific membrane antigen (PSMA) or folate hydrolase, is a metallopeptidase expressed predominantly in the human brain and prostate. GCPII expression is considerably increased in prostate carcinoma, and the enzyme also participates in glutamate excitotoxicity in the brain. Therefore, GCPII represents an important diagnostic marker of prostate cancer progression and a putative target for the treatment of both prostate cancer and neuronal disorders associated with glutamate excitotoxicity. For the development of novel therapeutics, mouse models are widely used. However, although mouse GCPII activity has been characterized, a detailed comparison of the enzymatic activity and tissue distribution of the mouse and human GCPII orthologs remains lacking. In this study, we prepared extracellular mouse GCPII and compared it with human GCPII. We found that mouse GCPII possesses lower catalytic efficiency but similar substrate specificity compared with the human protein. Using a panel of GCPII inhibitors, we discovered that inhibition constants are generally similar for mouse and human GCPII. Furthermore, we observed highest expression of GCPII protein in the mouse kidney, brain, and salivary glands. Importantly, we did not detect GCPII in the mouse prostate. Our data suggest that the differences in enzymatic activity and inhibition profile are rather small; therefore, mouse GCPII can approximate human GCPII in drug development and testing. On the other hand, significant differences in GCPII tissue expression must be taken into account when developing novel GCPII-based anticancer and therapeutic methods, including targeted anticancer drug delivery systems, and when using mice as a model organism.

• Publikační typ
• časopisecké články MeSH

Chronic constriction injury to the sciatic nerve was used as an animal model of neuropathic pain. Instead of frequently used reflex-based tests we used an operant thermal place preference test to evaluate signs of neuropathic pain and the effect of baclofen administration in rats with neuropathy. Chronic constriction injury was induced by four loose ligations of the sciatic nerve. Thermal place preference (45 °C vs. 22 °C and 45 °C vs. 11 °C) was measured after the ligation and after the administration of baclofen in sham and experimental rats. Rats with the chronic constriction injury spent significantly less time on the colder plate compared to sham operated animals at the combination 45 °C vs. 11 °C. After administration of baclofen (10 mg/kg s.c.), the aversion to the colder plate in rats with chronic constriction injury disappeared. At the combination 45 °C vs. 22 °C, no difference in time spent on colder and/or warmer plate was found between sham and experimental animals. These findings show the importance of cold allodynia evaluation in rats with chronic constriction injury and the effectiveness of baclofen in this neuropathic pain model.

• MeSH
• baklofen farmakologie   terapeutické užití   MeSH
• centrálně působící myorelaxancia farmakologie   terapeutické užití   MeSH
• konstrikce MeSH
• krysa rodu rattus MeSH
• měření bolesti metody   psychologie   MeSH
• nemoci periferního nervového systému farmakoterapie   psychologie   MeSH
• nemoci sedacího nervu farmakoterapie   psychologie   MeSH
• nízká teplota * MeSH
• operantní podmiňování účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• vysoká teplota * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• glifloziny MeSH
• klinické lékařství MeSH
• komplikace diabetu MeSH
• nemoci ledvin farmakoterapie   MeSH
• transportér 2 pro sodík a glukózu terapeutické užití   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• diabetologie
• nefrologie
• NLK Publikační typ
• kolektivní monografie

• MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• glifloziny MeSH
• lidé MeSH
• renální reabsorpce fyziologie   účinky léků   MeSH
• transportér 2 pro sodík a glukózu * farmakokinetika   terapeutické užití   MeSH
• transportní proteiny pro sodík a glukosu dějiny   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

Transient receptor potential melastatin-1 (TRPM1) is a calcium channel that is essential for the depolarization of photo-responsive retinal bipolar cells, but most of the physiological functions and cellular roles of this channel are still poorly understood. Most transient receptor potential (TRP) channels are typically regulated by intracellular proteins and other signaling molecules. Phosphatidylinositol-4,5 bisphosphate (PIP2), a minor phospholipid component of cell membranes, has previously been shown to directly bind TRP channels and to play a unique role in modulating receptor function. To characterize the binding of PIP2 as a potential regulator of TRPM1, we utilized biophysical methods and molecular modeling to study the interactions of PIP2 with an N-terminal fragment of TRPM1 (residues A451-N566). The basic N-terminal residue K464 of TRPM1 suggests that it is part of putative pleckstrin homology (PH) domain and is involved in the interactions with PIP2. This is the first report detailing the binding of PIP2 at the N-terminus of the TRPM1 receptor.

• MeSH
• cirkulární dichroismus MeSH
• fosfatidylinositol-4,5-difosfát chemie   metabolismus   MeSH
• kationtové kanály TRPM chemie   genetika   metabolismus   MeSH
• lidé MeSH
• povrchová plasmonová rezonance MeSH
• rekombinantní proteiny biosyntéza   chemie   izolace a purifikace   MeSH
• sekundární struktura proteinů MeSH
• simulace molekulární dynamiky MeSH
• terciární struktura proteinů MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• filtrační bariéra v glomerulech MeSH
• glifloziny MeSH
• glukoneogeneze fyziologie   MeSH
• hypoglykemika dějiny   metabolismus   terapeutické užití   MeSH
• krevní glukóza * metabolismus   MeSH
• ledviny * fyziologie   metabolismus   MeSH
• lidé MeSH
• proximální tubuly ledvin fyziologie   metabolismus   patofyziologie   MeSH
• transportér 2 pro sodík a glukózu dějiny   MeSH
• Check Tag
• lidé MeSH

The transient receptor potential melastatin 4 (TRPM4) is a calcium-activated non-selective ion channel broadly expressed in a variety of tissues. Receptor has been identified as a crucial modulator of numerous calcium dependent mechanisms in the cell such as immune response, cardiac conduction, neurotransmission and insulin secretion. It is known that phosphoinositide lipids (PIPs) play a unique role in the regulation of TRP channel function. However the molecular mechanism of this process is still unknown. We characterized the binding site of PIP2 and its structural analogue PIP3 in the E733-W772 proximal region of the TRPM4 N-terminus via biophysical and molecular modeling methods. The specific positions R755 and R767 in this domain were identified as being important for interactions with PIP2/PIP3 ligands. Their mutations caused a partial loss of PIP2/PIP3 binding specificity. The interaction of PIP3 with TRPM4 channels has never been described before. These findings provide new insight into the ligand binding domains of the TRPM4 channel.

• MeSH
• dimyristoylfosfatidylcholin analogy a deriváty   metabolismus   MeSH
• fosfatidylinositol-4,5-difosfát metabolismus   MeSH
• kationtové kanály TRPM chemie   metabolismus   MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• peptidové fragmenty chemie   metabolismus   MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• simulace molekulového dockingu MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH