AIM: The purpose of this project was to compare the characteristics of two experimental murine models of primary intraocular lymphoma (PIOL) and determine which experimental model is most suitable for further investigational research to elucidate the pathophysiology of PIOL and to find new therapeutical strategies. METHODS: In both experimental models PIOL was induced in immunocompetent mice with intravitreal injection of syngeneic B-cell lymphoma cell lines. Murine strain C3H/HeN and cell line 38C13 were used in the first model and BALB/CaNn mice and cell line A20 in the second model. During the experiments, thorough clinical evaluation (using photo documentation, ultrasonography, and MRI) and histological evaluation were performed. RESULTS: In both models, the percentage of PIOL development was high, reaching nearly 80%. Disease progression was faster in C3H/HeN with exophthalmos occurring on average on day 10. Vitreous involvement was a predominant sign in the clinical presentation of this group. In BALB/CaNn mice exophthalmos occurred on average on day 22. The predominant clinical sign in the BALB/CaNn group was tumorous infiltration of the retina, optic disc, and tumorous retinal detachment. CONCLUSION: Slower progression of the disease in BALB/CaNn mice, greater possibility to examine the retina due to mild vitreous involvement, and later occurrence of exophthalmos makes this strain more suitable for further investigational research.
- MeSH
- B-buněčný lymfom patologie MeSH
- modely nemocí na zvířatech * MeSH
- myši inbrední BALB C * MeSH
- myši inbrední C3H MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nitrooční lymfom * patologie MeSH
- progrese nemoci MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
INTRODUCTION: Nerve grafting with the sural nerve is a standard treatment method for radial nerve injury that requires another incision at the lateral ankle distal from the injured upper limb. The aim of this study was to investigate the common trunk (CTCB) of the inferior lateral brachial cutaneous nerve (ILBCN) and posterior antebrachial cutaneous nerve (PACN) as a possible donor inside the lateral intermuscular septum. MATERIALS AND METHODS: The arms and legs of 8 formalin-embalmed cadaver specimens were studied. The radial nerve, common trunk of the ILBCN and PACN, and the sural nerve were identified and measured in length and diameter. For histological examination, nerve samples from 6 fresh cadavers were harvested and processed for further axonal counting. RESULTS: The average length of the CTCB was 114.92 ± 18.9 mm. To match the diameter of the radial nerve at its proximal third, 3 cables of CTCB graft were necessary, which corresponds to a defect length of 3.8 cm. At the level of the distal third, the number of grafts was reduced to 2 with a corresponding defect length of 5.7 cm. The radial nerve contained 15162 ± 318 axons, and the CTCB comprised 3959 ± 176 axons. To match the axon count of the recipient nerve, 4 grafts of CTCB were necessary, which corresponded to a defect length of 2.8 cm. CONCLUSION: CTCB is a consistent and easily dissected cutaneous nerve branch of the radial nerve that can be used for bridging small gaps after neuroma-in-continuity in radial nerve palsy.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- mrtvola MeSH
- nervový transfer * metody MeSH
- nervus radialis * chirurgie anatomie a histologie zranění MeSH
- nervus suralis * transplantace anatomie a histologie MeSH
- senioři MeSH
- zákroky plastické chirurgie * metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The complexity of the galaninergic system is still not fully understood, especially under specific pre-existing comorbidities related to metabolic dysfunction. A plant-derived triterpenoid celastrol was demonstrated to exert a complex effect on the galaninergic system and to have hepatoprotective and anti-obesity properties. However, the exact molecular mechanisms responsible for these effects remain unclear. Specifically, there are no data on the impact of celastrol on the heart and liver galaninergic system. Therefore, this study aimed to investigate the effects of celastrol on the galaninergic system expression in the heart and liver of mice suffering from diet-induced obesity and metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD/MASH). METHODS: The male mice C57BL/6J were fed a Western-type high-fat diet for 16 and 20 weeks to induce obesity and MASLD/MASH. Celastrol was administered along with a specific diet for the last 4 weeks to evaluate its impact on the progression of these conditions. Moreover, the inhibitor of sterol regulatory element-binding protein 1/2 (SREBP1/2), fatostatin, was also tested to compare its influence on the galaninergic system with celastrol. RESULTS: The study demonstrates that celastrol treatment was safe and led to a reduction in food and energy intake, body fat and liver weights, and MASLD-to-MASH progression and improved glucose tolerance, serum biochemistry markers, and hepatic lipid peroxidation in mice. Quantitative gene expression originally showed significant regulation of galanin and all three of its receptors (GalR1/2/3) in the heart ventricles and only GalR2 in the liver of obese mice. Celastrol influenced the gene expression of galanin receptors: it downregulated Galr1 in the heart and upregulated Galr2 in the liver and Galr3 in the heart ventricles, potentially affecting energy metabolism, oxidative stress, and inflammation. Fatostatin suppressed gene expression of all the detected members of the galaninergic system in the heart ventricles, depicting the role of SREBP in this process. CONCLUSION: These findings suggest that celastrol may beneficially modulate the galaninergic system under obesity and MASLD-to-MASH progression, indicating its potential as a therapeutic agent for disorders associated with metabolic dysfunction.
- Publikační typ
- časopisecké články MeSH
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease with unknown cause. It mainly affects joints and, without proper treatment, negatively impacts their movement, causes painful deformities, and reduces the patients' quality of life. Current treatment options consist of various types of disease-modifying antirheumatic drugs (DMARDs), however 20-30% of patients are partially resistant to them. Therefore, development of new drugs is necessary. Possible option are compounds exhibiting their action via endocannabinoid system, which plays an important role in pain and inflammation modulation. One such compound - cannabidiol (CBD) has already been shown to attenuate synovitis in animal model of RA in in vivo studies. However, it has low bioavailability due to its low water solubility and lipophilicity. This issue can be addressed by preparation of a lipid containing formulation targeting lymphatic system, another route of absorption in the body. Materials and Methods: CBD-containing emulsion was prepared by high-shear homogenization and its droplet size distribution was analysed by optical microscopy. The relative oral bioavailability compared to oil solution as well as total availability of CBD were assessed in a cross-over study in rats and absorption of CBD via lymphatic system was observed. The effect of CBD on the animal model of RA was determined. Results: Compared to oil solution, the emulsion exhibited higher absolute oral bioavailability. Significant lymphatic transport of CBD was observed in all formulations and the concentrations in lymph were calculated. The therapeutic effect of CBD on RA was confirmed as an improvement in clinical symptoms as well as morphological signs of disease activity were observed during the study. Conclusion: In this work, we prepared a simple stable emulsion formulation, determined the pharmacokinetic parameters of CBD and calculated its absolute bioavailability in rats. Moreover, we successfully tested the pharmaceutical application of such a formulation and demonstrated the positive effect of CBD in an animal model of RA.
- MeSH
- aplikace orální MeSH
- bolest farmakoterapie MeSH
- emulze MeSH
- kanabidiol * farmakologie chemie MeSH
- klinické křížové studie MeSH
- krysa rodu rattus MeSH
- kvalita života MeSH
- revmatoidní artritida * farmakoterapie MeSH
- voda MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We aimed to prepare novel dibenzo [a,d][7]annulen derivatives that act on N-methyl-d-aspartate (NMDA) receptors with potential neuroprotective effects. Our approach involved modifying the tropane moiety of MK-801, a potent open-channel blocker known for its psychomimetic side effects, by introducing a seven-membered ring with substituted base moieties specifically to alleviate these undesirable effects. Our in silico analyses showed that these derivatives should have high gastrointestinal absorption and cross the blood-brain barrier (BBB). Our pharmacokinetic studies in rats supported this conclusion and confirmed the ability of leading compounds 3l and 6f to penetrate the BBB. Electrophysiological experiments showed that all compounds exhibited different inhibitory activity towards the two major NMDA receptor subtypes, GluN1/GluN2A and GluN1/GluN2B. Of the selected compounds intentionally differing in the inhibitory efficacy, 6f showed high relative inhibition (∼90 % for GluN1/GluN2A), while 3l showed moderate inhibition (∼50 %). An in vivo toxicity study determined that compounds 3l and 6f were safe at 10 mg/kg doses with no adverse effects. Behavioral studies demonstrated that these compounds did not induce hyperlocomotion or impair prepulse inhibition of startle response in rats. Neuroprotective assays using a model of NMDA-induced hippocampal neurodegeneration showed that compound 3l at a concentration of 30 μM significantly reduced hippocampal damage in rats. These results suggest that these novel dibenzo [a,d][7]annulen derivatives are promising candidates for developing NMDA receptor-targeted therapies with minimal psychotomimetic side effects.
- MeSH
- dizocilpinmaleát * farmakologie MeSH
- hematoencefalická bariéra metabolismus účinky léků MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- molekulární struktura MeSH
- neuroprotektivní látky * farmakologie chemie chemická syntéza MeSH
- potkani Sprague-Dawley MeSH
- receptory N-methyl-D-aspartátu * antagonisté a inhibitory metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Precise positioning of the acetabular component during total hip replacement is the key to achieving optimal implant function and ensuring long-term patient comfort. However, different anatomical variations, degenerative changes, dysplasia, and other diseases make it difficult. In this study, we discuss a method based on the three-dimensional direction of the transverse ligament, predicting native acetabular anteversion with higher accuracy. METHODS: Angular positions of the acetabulum and direction of the transverse ligament were automatically calculated from routine computed tomography data of 270 patients using a registration algorithm. The relationship between acetabular angles and ligament direction and their relationship with sex, age, and pelvic tilt were sought. These relationships were then modelled using multilinear regression. RESULTS: Including the direction of the transverse ligament in the sagittal and transverse planes as a regressor in the multilinear model explained the variation in acetabular anteversion (R2 = 0.76 for men, R2 = 0.63 for women; standard deviation in prediction: men, 3.92° and women, 4.00°). CONCLUSIONS: The results indicate that the ligament was suitable as a guidance structure almost insensitive to the ligament in the sagittal and transverse planes must be considered. Estimation based on the direction in only 1 plane was not sufficiently accurate. The operative acetabular inclination was not correlated with the direction of the ligament. The correlations were higher in men than in women.
- MeSH
- acetabulum * diagnostické zobrazování chirurgie MeSH
- anteverze kosti diagnostické zobrazování MeSH
- dospělí MeSH
- kloubní ligamenta * diagnostické zobrazování anatomie a histologie MeSH
- kyčelní kloub diagnostické zobrazování anatomie a histologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhrada kyčelního kloubu * metody MeSH
- počítačová rentgenová tomografie * MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- zobrazování trojrozměrné MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Total hip (THA) or knee (TKA) arthroplasty is still a traumatic and challenging operation that induces inflammation, with a particularly high risk of acute-phase reaction. The aim of this study was to predict the likelihood of implant-associated complications during the preoperative and postoperative course. METHODS: The prospective observational, non-interventional study of patients diagnosed with primary knee or hip osteoarthrosis undergoing THA or TKA during the study period was conducted. The inflammatory and malnutrition parameters were collected for each patient one day before surgery, two days after surgery, and in outpatient follow-up. RESULTS: Of 159 patients analysed, 12 developed implant-associated complications. The albumin, prealbumin, Intensive Care Infection Score (ICIS), Nutritional Risk Index, and white blood cell counts were found to be potential predictors. Notably, preoperative albumin levels significantly differed between groups with and without complications (P-value = 0.042). CONCLUSION: Our study definitively shows that WBC, prealbumin, Nutritional Risk Index, ICIS as a novel marker, and significantly albumin, outperform C-reactive protein in predicting implant-associated complications in hip and knee arthroplasty.
- MeSH
- artróza kyčelních kloubů chirurgie MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhrada kyčelního kloubu * škodlivé účinky MeSH
- pooperační komplikace * etiologie krev MeSH
- prealbumin metabolismus analýza MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sérový albumin analýza metabolismus MeSH
- totální endoprotéza kolene * škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
