Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo.

• Klíčová slova
• Usher syndrome, gene therapy, impaired vision, photoreceptor morphology, pig model,
• MeSH
• cytoskeletální proteiny MeSH
• fotoreceptory MeSH
• lidé MeSH
• prasata MeSH
• proteiny buněčného cyklu genetika   MeSH
• Usherovy syndromy * genetika   metabolismus   terapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytoskeletální proteiny MeSH
• proteiny buněčného cyklu MeSH

• MeSH
• chování zvířat * MeSH
• Haplorrhini MeSH
• hypnóza MeSH
• klasické podmiňování MeSH
• kočky MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• neurotické poruchy etiologie   MeSH
• operantní podmiňování MeSH
• ovce MeSH
• prasata MeSH
• psi MeSH
• psychický stres patofyziologie   MeSH
• psychologické modely MeSH
• psychotropní léky farmakologie   MeSH
• vačicovití MeSH
• záchvaty MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• psychotropní léky MeSH

Neuronal activity in the medulla oblongata and neurogenic inflammation of airways were investigated in a guinea pig model induced by repeated intra-esophageal instillation of hydrochloric acid (HCl) after vagotomy. Unilateral vagotomy was performed in the vagotomy group, while a sham-operation was performed in the sham group. Operation was not conducted in sham control group. Airway inflammation was observed with hematoxylin and eosin (HE) staining. C-fos protein was measured by immunohistochemistry (IHC) and Western blot (WB). Substance P was examined by IHC and enzyme-linked immuno sorbent assay (ELISA). Airway microvascular permeability was detected by evans blue dye (EBD) fluorescence. Inflammation of airway was observed in the trachea and bronchi after chronic HCl perfusion into the lower esophagus, and was alleviated after unilateral vagotomy. C-fos expression in the medulla oblongata was lower in the vagotomy group compared to the sham control and sham groups. Substance P-like immunoreactivity (SP-li), concentration and microvascular leakage in airway were lower in the vagotomy group than that in the other groups. Our results suggest that vagotomy improved neurogenic inflammation of airways and decreased neuronal activities, the afferent nerves and neurons in medulla oblongata may be involved in neurogenic inflammation of airways mediated by esophageal-bronchial reflex.

• MeSH
• abnormální reflex MeSH
• aspirační pneumonie chemicky indukované   patofyziologie   chirurgie   MeSH
• ezofágus inervace   MeSH
• kapilární permeabilita MeSH
• kyselina chlorovodíková * MeSH
• medulla oblongata metabolismus   patofyziologie   MeSH
• morčata MeSH
• neurogenní zánět chemicky indukované   patofyziologie   chirurgie   MeSH
• plíce inervace   metabolismus   MeSH
• protoonkogenní proteiny c-fos metabolismus   MeSH
• substance P metabolismus   MeSH
• vagotomie * MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina chlorovodíková * MeSH
• protoonkogenní proteiny c-fos MeSH
• substance P MeSH

Gastric dysmotility can be a sign of common diseases such as longstanding diabetes mellitus. It is known that the application of high-frequency low-energetic stimulation can help to effectively moderate and alleviate the symptoms of gastric dysmotility. The goal of the research was the development of a miniature, endoscopically implantable device to a submucosal pocket. The implantable device is a fully customized electronic package which was specifically designed for the purpose of experiments in the submucosa. The device is equipped with a lithium-ion battery which can be recharged wirelessly by receiving an incident magnetic field from the charging/transmitting coil. The uplink communication is achieved in a MedRadio band at 432 MHz. The device was endoscopically inserted into the submucosal pocket of a live domestic pig used as an in vivo model, specifically in the stomach antrum. The experiment confirmed that the designed device can be implanted into the submucosa and is capable of bidirectional communication. The device can perform bipolar stimulation of muscle tissue.

• MeSH
• bezdrátová technologie MeSH
• design vybavení * MeSH
• elektrostimulační terapie přístrojové vybavení   MeSH
• gastrointestinální endoskopie metody   MeSH
• gastroparéza terapie   MeSH
• implantabilní neurostimulátory * MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aims were to explore the effect of head-up tilt (HUT) to 30 and 60 degrees on hemodynamics and tissue oxygenation in anesthetized healthy swine. The data serve as a reference for a study of resuscitation efficacy at HUT such as during transport. Nine healthy swine (49+/-4 kg) were anesthetized and multiple sensors including myocardial pressure-volume loops catheter, carotid flow probe, blood pressure catheters, near infrared spectroscopy (NIRS) tissue oximetry and mixed venous oximetry (SVO2) catheter were introduced and parameters continuously recorded. Experimental protocol consisted of baseline in supine position (15 min), 30 degrees HUT (15 min), recovery at supine position (15 min) and 60 degrees HUT (5 min). Vacuum mattress was used for body fixation during tilts. We found that 30 and 60 degrees inclination led to significant immediate reduction in hemodynamic and oximetry parameters. Mean arterial pressure (mm Hg) decreased from 98 at baseline to 53 and 39, respectively. Carotid blood flow dropped to 47 % and 22 % of baseline values, end diastolic volume to 49 % and 53 % and stroke volume to 47 % and 45 % of baseline. SVO2 and tissue oximetry decreased by 17 and 21 percentage points. The values are means. In conclusions, within minutes, both 30 and 60 degrees head-up tilting is poorly tolerated in anesthetized swine. Significant differences among individual animals exist.

• MeSH
• arteriae carotides patofyziologie   MeSH
• arteriální tlak MeSH
• blízká infračervená spektroskopie MeSH
• časové faktory MeSH
• celková anestezie * MeSH
• hemodynamika * MeSH
• kyslík krev   MeSH
• modely u zvířat MeSH
• ortostatická intolerance krev   patofyziologie   MeSH
• oxymetrie metody   MeSH
• postura těla * MeSH
• prasata MeSH
• regionální krevní průtok MeSH
• spotřeba kyslíku MeSH
• supinační poloha MeSH
• test na nakloněné rovině MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyslík MeSH

• MeSH
• analgetika terapeutické užití   MeSH
• analgezie MeSH
• bolest chemicky indukované   diagnóza   farmakoterapie   prevence a kontrola   MeSH
• bradykinin farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• elektronika MeSH
• formaldehyd farmakologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech * MeSH
• morčata MeSH
• myši MeSH
• noha (od hlezna dolů) MeSH
• preklinické hodnocení léčiv metody   MeSH
• psi MeSH
• serotonin farmakologie   MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• morčata MeSH
• myši MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• analgetika MeSH
• bradykinin MeSH
• formaldehyd MeSH
• serotonin MeSH

OBJECTIVES: Alarmin high mobility group box 1 (HMGB1) is essential for correct DNA folding and transcription. It can be released from damaged cells or secreted by stimulated cells. HMGB1 has been detected in serum or plasma as a late marker of sepsis, but its suitability as a marker of sepsis has been disputed. METHODS: One-week-old germ-free piglets were orally infected/colonized with enteric bacterial pathogens (Salmonella Typhimurium or Escherichia coli O55) or with probiotic bacteria (E. coli Nissle 1917) for 24 h. The transcriptions of HMGB1, interleukin (IL)-8, tumor necrosis factor (TNF)-α, and IL-10 (quantitative reverse transcription and polymerase chain reaction), their protein levels (ELISA), and clinical state of the piglets (somnolence, anorexia, diarrhea, tachycardia, tachypnea, and tremor) were estimated. RESULTS: The piglets infected with enteric pathogens suffered from infections. HMGB1 was transcribed in the terminal ileum constitutively, regardless of any bacterial presence. In contrast, the transcription of cytokines was upregulated by virulent bacteria. HMGB1, IL-8, and TNF-α levels in the ileum were increased by both enteric pathogens, while IL-10 levels increased in E. coli O55-infected piglets only. HMGB1 significantly increased in the plasma of piglets infected with virulent E. coli only, but cytokine levels were in most cases increased by both virulent bacteria. HMGB1 and cytokine levels in ileum lavages and plasma of piglets colonized with probiotic E. coli remained comparable to those of the non-stimulated germ-free piglets. CONCLUSION: The local and systemic expression of HMGB1, its relationship to the inflammatory cytokines, and clinical findings showed HMGB1 as a suitable marker of severity of sepsis in the gnotobiotic piglet infection model.

• MeSH
• bakteriální infekce krev   imunologie   mikrobiologie   MeSH
• biologické markery krev   MeSH
• ELISA MeSH
• Escherichia coli růst a vývoj   MeSH
• gnotobiologické modely * MeSH
• ileum metabolismus   mikrobiologie   MeSH
• interleukin-10 krev   MeSH
• interleukin-8 krev   MeSH
• modely nemocí na zvířatech MeSH
• novorozená zvířata krev   imunologie   mikrobiologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prasata MeSH
• protein HMGB1 * krev   MeSH
• průjem MeSH
• Salmonella typhimurium růst a vývoj   MeSH
• sepse krev   imunologie   mikrobiologie   MeSH
• stupeň závažnosti nemoci MeSH
• tachykardie MeSH
• TNF-alfa krev   MeSH
• tremor MeSH
• zánět krev   imunologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• interleukin-10 MeSH
• interleukin-8 MeSH
• protein HMGB1 * MeSH
• TNF-alfa MeSH