PURPOSE OF THE STUDY: The preclinical study aimed to compare the healing of segmental bone defects treated with biodegradable hyaluronic acid and tricalcium phosphate-based hydrogel with the established autologous spongioplasty. Another aim was to evaluate the hydrogel as a scaffold for osteoinductive growth factor of bone morphogenetic protein-2 (BMP-2) and stem cells. MATERIAL AND METHODS: The study was conducted in an in vivo animal model. A standardized rabbit model of a 15 mm long segmental bone defect of left radius was used. A total of 40 animals were divided into 5 groups of 8 individuals. In the KO- (negative control) group, the created defect was left to heal spontaneously. In the KO+ (positive control) group, the defect was filled with morselized bone autograft prepared from the resected segment. In the study group A, the defect was filled with hydrogel based on hyaluronic acid derivative and tricalcium phosphate. In the study group B, the defect was filled with hydrogel based on hyaluronic acid derivative, tricalcium phosphate and bone marrow aspirate. In the study group C, the defect was filled with hydrogel based on hyaluronic acid derivative, tricalcium phosphate, bone marrow aspirate and BMP-2. Healing was assessed using radiographs at 1, 6, and 12 weeks postoperatively and histology specimens were collected at 16 weeks postoperatively. RESULTS: Altogether 35 rabbits survived (KO- 7, KO+ 7, A 7, B 6, C 8) until the end of the study. As concerns the radiographic assessment, the best results were achieved by the groups KO+ and C, where new bone formation across the entire width of the bone defect was clearly seen at 6 and 12 weeks and the osteotomy line was completely healed too. At 12 weeks, complete bone remodelling was observed in all animals in the group KO+, whereas in the group C, bone remodelling was fully completed in 5 animals and partially completed in 3 animals. In terms of histological assessment, however, the best results were achieved by the group C, where the bone defect was completely remodelled into lamellar bone in 7 specimens, while in 1 specimen it healed with bony callus formation. In the group KO+, the defect was healed in 4 specimens by cartilaginous callus with loci of remodelling into bony callus, in 2 specimens the bony callus was predominant with cartilaginous callus areas, and only one defect was completely remodelled into lamellar bone. DISCUSSION: Compared to autografts that manifest osteogenic, osteoinductive and osteoconductive properties, the biodegradable hyaluronic acid and tricalcium phosphate-based hydrogel has osteoconductive properties only. Thus, it was also tested in our study as a scaffold for bone marrow cells and BMP-2 osteoinductive growth factor. Thanks to its semi-liquid properties, the biodegradable hyaluronic acid and tricalcium phosphate-based hydrogel is a promising material for use in 3D printing. CONCLUSIONS: The preclinical study in an in vivo animal model confirmed the beneficial effect of the biodegradable hyaluronic acid and tricalcium phosphate-based hydrogel on the healing of critical-size segmental bone defects. Better healing of these defects was also confirmed for filling composed of hydrogel and BMP-2 osteoinductive growth factor. The benefit of bone marrow aspirate mixed with hydrogel was not confirmed. KEY WORDS: bone defect, non-union, rabbit, hyaluronic acid, calcium phosphate, stem cells, BMP-2, scaffold, bone healing, spongioplasty.

• MeSH
• fosforečnany vápenaté * farmakologie   MeSH
• hydrogely farmakologie   MeSH
• kostní morfogenetický protein 2 * MeSH
• králíci MeSH
• kyselina hyaluronová * farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• radius chirurgie   zranění   MeSH
• regenerace kostí účinky léků   MeSH
• tkáňové podpůrné struktury * MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

By December 2019, humanity was challenged by a new infectious respiratory disease named coronavirus disease of 2019 or COVID-19. This is a viral infection based on the presence of the previously non-problematic coronavirus with assigned number 2. This virus causes severe acute respiratory distress and is known now as SARS-CoV2. Since SARS-CoV2 is an RNA virus, remdesivir and favipiravir, both broad-spectrum RNA polymerase inhibitors, were repurposed for treating COVID-19 patients. Remdesivir and favipiravir are antimetabolites, and they are structurally related to the naturally occurring structural elements of RNA. Both agents are prodrugs and must be activated intracellularly to exert their effects through numerous and different mechanisms of action. Efforts have been exerted to determine their efficacy and safety against COVID-19 through clinical trials. Clinical trials have shown an association of remdesivir with increased frequency of adverse effects (in comparison to favipiravir). Nevertheless, the data obtained with remdesivir resulted in its approval by the FDA on the 22nd of October 2020 for COVID-19 treatment. At present, remdesivir is being recommended by several treatment guidelines for the treatment of COVID-19 patients. The evidence in favor of favipiravir is compromised by the small number and low-quality of trials conducted. Favipiravir has shown various benefits when administered in mild and moderate cases of COVID-19, while remdesivir was more beneficial in more severe cases of the disease. Since the two agents are suitable for different groups of patients, both drugs can play a significant role in fighting this pandemic. The goal of this work is to summarize the information available on two antimetabolites - remdesivir and favipiravir - and to compare clinical experience obtained so far with these two agents in COVID-19 patients.

• MeSH
• adenosinmonofosfát analogy a deriváty   farmakologie   terapeutické užití   MeSH
• alanin analogy a deriváty   MeSH
• amidy MeSH
• COVID-19 * MeSH
• farmakoterapie COVID-19 MeSH
• lidé MeSH
• pyraziny MeSH
• RNA virová MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The search for tacrine derivatives, as potential Alzheimer´s disease treatment, is still being at the forefront of scientific efforts. 7-MEOTA was found to be a potent, centrally active acetylcholinesterase inhibitor free of the serious side effects observed for tacrine. Unfortunately, a relevant argumentation about pharmacokinetics and potential toxicity is incomplete; information about tacrine derivatives absorption and especially CNS penetration are still rare as well as detailed toxicological profile in vivo. Although the structural changes between these compounds are not so distinctive, differences in plasma profile and CNS targeting were found. The maximum plasma concentration were attained at 18th min (tacrine; 38.20 ± 3.91 ng/ml and 7-MEOTA; 88.22 ± 15.19 ng/ml) after i.m. application in rats. Although the brain profiles seem to be similar; tacrine achieved 19.34 ± 0.71 ng/ml in 27 min and 7-MEOTA 15.80 ± 1.13 ng/ml in 22 min; the tacrine Kp (AUCbrain/AUCplasma) fit 1.20 and was significantly higher than 7-MEOTA Kp 0.10. Administration of tacrine and 7-MEOTA showed only mild elevation of some biochemical markers following single p.o. application in 24 hours and 7 days. Also histopathology revealed only mild-to-moderate changes following repeated p.o. administration for 14 days. It seems that small change in tacrine molecule leads to lower ability to penetrate through the biological barriers. The explanation that lower p.o. acute toxicity of 7-MEOTA depends only on differences in metabolic pathways may be now revised to newly described differences in pharmacokinetic and toxicological profiles.

• MeSH
• časové faktory MeSH
• cholinesterasové inhibitory aplikace a dávkování   farmakokinetika   toxicita   MeSH
• krysa rodu rattus MeSH
• mozek metabolismus   MeSH
• plocha pod křivkou MeSH
• potkani Wistar MeSH
• takrin aplikace a dávkování   analogy a deriváty   farmakokinetika   toxicita   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Dirofilaria repens and Dirofilaria immitis are the most common filarial species affecting humans in Europe. Dirofilaria repens causes subcutaneous or ocular infection, whereas D. immitis is responsible mainly for the pulmonary form. In this report, we present the first human case of periorbital dirofilariasis in the Czech Republic. A 58-year-old woman suffered from an eyelid oedema, redness and pain in the left eye. After excising the parasite from her eyelid, all clinical symptoms disappeared. Based on the morphology and cytochrome oxidase I sequencing, the parasite was identified as D. repens. Histology revealed that the excised worm was female with absent microfilariae in uteri. With respect to the length of the incubation period and the sequence identity with a known Czech isolate, we concluded that D. repens was most likely of autochthonous origin.

• MeSH
• cyklooxygenasa 1 genetika   MeSH
• Dirofilaria repens cytologie   genetika   izolace a purifikace   MeSH
• dirofilarióza parazitologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrofilárie izolace a purifikace   MeSH
• oční infekce parazitární parazitologie   patologie   MeSH
• proteiny červů genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Geografické názvy
• Česká republika MeSH

To evaluate the preclinical efficacy and safety of human mesenchymal stem cells (hMSC) rapidly expanded in growth medium for clinical use with human serum and recombinant growth factors, we conducted a controlled, randomized trial of plasma clots with hMSC vs. plasma clots only in critical segmental femoral defects in rnu/rnu immunodeficient rats. X-ray, microCT and histomorphometrical evaluation were performed at 8 and 16 weeks. MSC were obtained from healthy volunteers and patients with lymphoid malignancy. Human MSC survived in the defect for the entire duration of the trial. MSC from healthy volunteers, in contrast to hMSC from cancer patients, significantly improved bone healing at 8, but not 16 weeks. However, at 16 weeks, hMSC significantly improved vasculogenesis in residual defect. We conclude that hMSC from healthy donors significantly contributed to the healing of bone defects at 8 weeks and to the vascularisation of residual connective tissue for up to 16 weeks. We found the administration of hMSC to be safe, as no adverse reaction to human cells at the site of implantation and no evidence of migration of hMSC to distant organs was detected.

• MeSH
• dospělí MeSH
• femur diagnostické zobrazování   fyziologie   MeSH
• hojení ran fyziologie   MeSH
• krysa rodu rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezenchymální kmenové buňky fyziologie   MeSH
• náhodné rozdělení MeSH
• osteogeneze fyziologie   MeSH
• počítačová rentgenová tomografie metody   MeSH
• potkani nazí MeSH
• senioři MeSH
• syndromy imunologické nedostatečnosti diagnostické zobrazování   imunologie   terapie   MeSH
• transplantace mezenchymálních kmenových buněk metody   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• souhrny MeSH

Uterine lymphoma is rare in the dog, in other animal species, and in humans. The lymphoma in the two female dogs presented as a primary tumour of uterine tissue and was classified as diffuse centroblastic B cell lymphoma. Terminally, the uterine lymphoma metastasized to various organs in one of the dogs, despite chemotherapy. This case study describes a very rare form of canine lymphoma and suggests to include lymphoma in the differential diagnoses in bitches with uterine masses.

• MeSH
• B-buněčný lymfom * MeSH
• nádory močového měchýře MeSH
• nemoci psů * MeSH
• Publikační typ
• kazuistiky MeSH

Lidské mezenchymové stromální buňky (hMSC) budou připravovány z kostní krve pacientů podstupujících vyšetření kostní dřeně z diagnostických důvodů a expandovány patentovanou metodou vyvinutou předkladateli grantového projektu. Dosavadní znalosti farmakodynamiky budou doplněny studiemi zaměřenými na průkaz konceptu, charakterizaci buněk a testy bezpečnosti in vivo a in vitro. Patentovaný způsob kultivace bude přenesen do podmínek správné výrobní praxe (GMP). Dále bude vytvořena preklinická dokumentace týkající se komponent užívaných k přípravě buněčného preparátu. Optimalizovaná metodika expanze hMSC bude následně předložena k posouzení Státnímu ústavu pro kontrolu léčiv (SUKL), eventuálně po připomínkách SUKL doplněna tak, aby přípravek mohl být schválen pro užití v klinických studiích.; Human mesenchymal stromal cells (hMSC) will be prepared form bone blood of patients undergoing bone marrow examination for diagnostic purposes and will be expanded by patented method developed by submitters of the grant project proposal. Previously obtained knowledge of pharmacodynamics will be completed with studies performed to proof the concept, to characterize the cells and to test safety of the cellular product in vitro and in vivo. Patented method of cultivation will be transferred to conditions of good manufacturing practice (GMP). Preclinical documentation concerning components used for preparation of the cellular product will be compiled and request for approval of the product for clinical use will be submitted to the Czech State Institute for Drug Control (SÚKL) to obtain approval for clinical use. If necessary, documentation will be completed to conform with SUKL requirements.

• MeSH
• dokumentace MeSH
• farmakokinetika MeSH
• hodnocení léčiv MeSH
• kultivační techniky MeSH
• mezenchymální kmenové buňky MeSH
• schvalování léčiv MeSH
• vyšetřování kostní dřeně MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• farmacie a farmakologie
• lékařství
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Purpose: The aim of our study was to determine and compare the activity of acetylcholinesterase (AChE) in different parts of dog brain after the exposure to nerve agent sarin with or without HI-6 oxime treatment. Material and methods: Before intoxication, beagle dogs were intravenously anaesthetized and premedicated with atropine sulphate (0.01 mg/kg). Three experimental groups were established – control, sarin (0.03 mg/kg, intramuscularly, 5 min after anaesthesia onset), and sarin + HI-6 dichloride (11.4 mg/kg, intramuscularly, 30 min after sarin poisoning). Brain (amygdaloid body, head of caudate nucleus, somatosensory cortex, Amon’s horn of hippocampus, hypothalamus, brain stem ventral respiratory group, and medial nuclei of thalamus) samples were taken 4 h after sarin administration. AChE activity was detected by histochemistry using the Karnovsky-Roots method and computer image analysis. Results: Sarin poisoning decreased AChE activity in all selected brain areas. HI-6 did not affect this outcome. Conclusion: HI-6 does not reactivate brain AChE in dogs when administered 30 min after sarin poisoning.

• MeSH
• antidota * farmakologie   MeSH
• cholinesterasové inhibitory otrava   MeSH
• histologické techniky MeSH
• modely nemocí na zvířatech MeSH
• mozek * enzymologie   patologie   MeSH
• pralidoximové sloučeniny farmakologie   terapeutické užití   MeSH
• psi MeSH
• pyridinové sloučeniny farmakologie   terapeutické užití   MeSH
• sarin * otrava   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• psi MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH