Previously, we demonstrated that supplementation of resuscitation fluids with the Kv7 voltage-activated potassium channel inhibitor linopirdine reduces fluid resuscitation requirements and stabilizes hemodynamics in various rat models of hemorrhagic shock. To further evaluate the therapeutic potential of linopirdine, we tested the effects of linopirdine-supplemented resuscitation fluids in a rat model of ischemia-reperfusion injury-induced acute respiratory distress syndrome (ARDS). Ventilated rats underwent unilateral lung ischemia from t=0-75 min, followed by lung reperfusion and fluid resuscitation to a mean arterial blood pressure of 60 mmHg with normal saline (NS, n=9) or NS supplemented with 50 μg/ml linopridine (NS-L), n=7) until t=360 min. As compared with NS, fluid resuscitation with NS-L stabilized blood pressure and reduced fluid requirements by 40% (p<0.05 vs. NS at t=240-360 min). While NS-L did not affect ARDS development, it reduced mortality from 66% with NS to 14% with NS-L (p=0.03, hazard ratio 0.14; 95% confidence interval of the hazard ratio: 0.03-0.65). Median survival time was 240 min with NS and >360 min with NS-L. As compared with NS treated animals that survived the observation period (n=3), however, plasma lactate and creatinine concentrations at t=360 min were higher with NS-L (n=6; p<0.05). Our findings extend therapeutic potential of NS-L from hypovolemic/hemorrhagic shock to hemodynamic instability under normovolemic conditions during organ ischemia-reperfusion injury. Possible adverse effects of NS-L, such as impairment of renal function and/or organ hypoperfusion, require further evaluation in long-term pre-clinical models.
- MeSH
- blokátory draslíkových kanálů aplikace a dávkování MeSH
- časové faktory MeSH
- indoly aplikace a dávkování MeSH
- intravenózní infuze MeSH
- krevní tlak účinky léků MeSH
- modely nemocí na zvířatech MeSH
- potkani Sprague-Dawley MeSH
- pyridiny aplikace a dávkování MeSH
- reperfuzní poškození komplikace MeSH
- resuscitace * MeSH
- solný roztok aplikace a dávkování MeSH
- syndrom dechové tísně etiologie patofyziologie terapie MeSH
- tekutinová terapie * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Intestinal ischemic-reperfusion (IR) injury has detrimental effects on both local and distant organs in the body. Betanin is known for its antioxidant properties, and it is found mostly in vegetables. Therefore, the aim of the present study was to test the hypothesis that betanin administration prior intestinal IR, may be beneficial in protecting jejunal mucosa and lung parenchyma against IR damage. Male specific pathogen-free Charles River Wistar rats were used (n = 42). Betanin (50 mg/kg) was administered intraperitoneally 30 min before ischemia of the superior mesenteric artery lasting 1 h, followed by 1, 4 and 24 h of reperfusion. Immunohistochemical as well as histomorphometrical analysis indicated a protective effect of betanin pretreatment on jejunal tissue. Regarding morphometrical analysis betanin significantly (p < 0.01) augments intestinal villus height after 24 of reperfusion comparing to early stages. Betanin application reduced number of mast cells population in early reperfusion periods (p < 0.05). The protective effect of betanin on lung parenchyma, was detected in late reperfusion period (24 h) with improvement of histopathological injury index and morphometric analysis (p < 0.001 for both). The improvement of histopathological injury index (p < 0.001) and morphometric analysis (p < 0.001) during the late reperfusion period, suggests a protective effect of betanin on lung parenchyma. Moreover, suppression of the inflammatory response was mirrored by the reduction of myeloperoxidase (MPO) positive cells within lung parenchyma after 1 and 4 h of reperfusion (p < 0.001). Especially, during the first 4 h of reperfusion after betanin administration, a reduction of 74% of the polymorphonuclear neutrophils infiltration (MPO positive cell population) and of a nearly 46% of active MCs was observed. Upon morphometric examination, the lung histological architecture after 24 h of reperfusion appeared to be almost 100% better following betanin treatment, with 25% thinner interalveolar septa and 20% larger alveolar surface for respiratory gas exchange. The results suggest that betanin pretreatment protects the jejunal mucosa and the lung parenchyma, as well as reduces the inflammatory cell density after intestinal IR injury.
- MeSH
- betakyaniny aplikace a dávkování farmakologie MeSH
- jejunum účinky léků zranění patologie MeSH
- krysa rodu rattus MeSH
- parenterální výživa MeSH
- plíce účinky léků patologie MeSH
- potkani Wistar MeSH
- reperfuzní poškození komplikace MeSH
- zánět farmakoterapie etiologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Delayed graft function (DGF) caused by ischemia/reperfusion injury (I/RI) negatively influences the outcome of kidney transplantation. This prospective single-center study characterized the intrarenal transcriptome during I/RI as a means of identifying genes associated with DGF development. METHODS: Characterization of the intrarenal transcription profile associated with I/RI was carried out on three sequential graft biopsies from respective allografts before and during transplantation. The intragraft expression of 92 candidate genes was measured using quantitative real-time reverse transcriptase polymerase chain reaction (2) in delayed (n=9) and primary function allografts (n=26). RESULTS: Cold storage was not associated with significant changes to the expression profile of the target gene transcripts; however, up-regulation of 16 genes associated with enhanced activation of innate and adaptive immune responses and apoptosis was observed after reperfusion. Multivariate logistic regression analysis revealed that higher tubular atrophy scores (ct) together with a lower expression of Netrin-1 might predict DGF development (training area under the receiver operating curve=0.89, cross-validated area under the receiver operating curve=0.81). CONCLUSIONS: Poor baseline tubular cell quality (defined by a higher rate of tubular atrophy) combined with the reduced potential of apoptotic survival factors represented by decreased Netrin-1 gene expression were associated with delayed kidney graft function.
- MeSH
- analýza hlavních komponent MeSH
- atrofie MeSH
- biopsie MeSH
- imunohistochemie MeSH
- ledvinové kanálky patologie MeSH
- lidé MeSH
- logistické modely MeSH
- nádorové supresorové proteiny analýza genetika MeSH
- neurotrofní faktory analýza genetika MeSH
- opožděný nástup funkce štěpu etiologie metabolismus patologie MeSH
- prospektivní studie MeSH
- regulace genové exprese MeSH
- reperfuzní poškození komplikace MeSH
- transplantace ledvin škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Recent studies demonstrated remote effects of renal ischemia/reperfusion (I/R) injury on some organs such as brain, liver, and lungs. We investigated the effects of renal I-R injury on function, histology and oxidative stress state of pancreas. Twenty-four male adult Sprague-Dawley rats were divided equally into 2 groups; sham group: rats underwent midline laparotomy and dissection of renal pedicles without renal ischemia, and ischemic group: rats underwent bilateral renal ischemia for 45 min. Renal functions (serum creatinine and BUN), pancreatic functions (serum amylase, lipase and insulin) and fasting blood glucose were measured at 2 h, 1 day, 3 days and 7 days after ischemia. Also, pancreatic histology and malondialdehyde (MDA), catalase and reduced glutathione (GSH) were examined at 2 h and 7 days after ischemia. The ischemic rats showed significant increase in serum creatinine and BUN with significant increase in serum amylase and lipase at 2 h, 1 day and 3 days after ischemia. Blood glucose and fasting insulin showed no significant change apart from significant increase in insulin in sham group at 1 day after ischemia. Pancreas isolated from ischemic rats showed significant increase in histopathological damage score and significant increase in MDA and catalase enzyme with decrease in GSH. In conclusion, bilateral renal ischemia for 45 min caused significant impairment of pancreatic functions and histology. This might be due to deficiency of antioxidant and increased lipid peroxidations in pancreatic tissues.
- MeSH
- akutní poškození ledvin komplikace metabolismus patologie MeSH
- krysa rodu rattus MeSH
- náhodné rozdělení MeSH
- oxidační stres fyziologie MeSH
- pankreas zranění metabolismus patologie MeSH
- potkani Sprague-Dawley MeSH
- reperfuzní poškození komplikace metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
V období do 3 měsíců po transplantaci jater představuje cholestáza různého typu a stupně 1 z nejčastějších morfologických nálezů v biopsiích jaterních štěpů. Morfologii cholestázy sdílejí nejen všechny varianty onemocnění s poškozením žlučovodů, ale i další onemocnění s těžším postižením hepatocytů včetně rejekce a rekurence virových hepatitid. Bioptická diagnostika je zlatým standardem při řešení příčin dysfunkce štěpu jater a ve velké většině případů umožňuje odlišit hlavní kategorie chorob vedoucí k cholestáze. V časném období po transplantaci jater se na poškození štěpu obvykle podílí kombinace různých příčin. Proto je interpretace omezených morfologických znaků, které většinou představují určitý typ tkáňové reakce a nikoli noxu, komplikovaná. Nezbytným předpokladem pro co nejlepší interpretaci morfologického závěru se stává úzká spolupráce hepatologa a patologa.
During the first three months after a liver transplant, cholestasis of various type and degree represents 1 of the most frequent morphological findings in liver graft biopsies. The morphology of cholestasis is typical for all conditions with bile duct impairment but also for other conditions with more severe impairment of hepatocytes, including rejection and recurrence of viral hepatitides. Histological diagnosis represents the gold standard in addressing liver graft dysfunction causes, and in the majority of cases it allows for distinguishing between the main categories of diseases resulting in cholestasis. Usually a combination of various changes can be identified as a cause of the liver graft dysfunction early after transplantation. Therefore, the interpretation of limited morphological characteristics, which usually represent a certain type of tissue reaction, not the cause, is complicated. The close cooperation between the hepatologist and pathologist has become a necessary prerequisite for the best possible interpretation of the morphological conclusion.
- Klíčová slova
- fibrocholestatická hepatitida,
- MeSH
- biopsie * MeSH
- cholestáza diagnóza etiologie patologie MeSH
- diferenciální diagnóza MeSH
- hepatitida B diagnóza komplikace patologie MeSH
- hepatitida C diagnóza komplikace patologie MeSH
- hepatocyty patologie MeSH
- játra patologie MeSH
- lidé MeSH
- pooperační komplikace * diagnóza etiologie patologie MeSH
- rejekce štěpu diagnóza komplikace patologie MeSH
- reperfuzní poškození diagnóza komplikace patologie MeSH
- stenóza diagnóza komplikace MeSH
- transplantace jater * škodlivé účinky MeSH
- žlučové cesty patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Curcumin, a component of the spice turmeric, was shown to have a protective effect on acute kidney injury markers following ischemia-reperfusion injury (IRI). However, its effect on glomerular and tubular renal functions following IRI is not known and this data is probably of more clinical relevance. In this study, curcumin was tested for its effect on renal functional parameters following two different periods of warm IRI in the rat. Groups V-30 (n=10) and C-30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45 (n=8) underwent ischemia for 45 minutes. C-30 and C-45 received oral curcumin (200 mg/kg/day) whereas V-30 and V-45 received a vehicle. The left renal artery blood flow was measured by a flowmeter before and 15 minutes after reperfusion. Serum TNF-alpha was measured before and 2 days after ischemia. The function of both kidneys was measured 2 days following ischemia using clearance technique. IRI caused significant increase in TNF-alpha in all groups. Curcumin significantly ameliorated the ischemia-induced alterations in serum TNF-alpha and associated histological changes but did not affect the alterations in renal artery blood flow, glomerular (glomerular filtration rate, renal blood flow) or tubular (urinary volume, urinary sodium and fractional excretion of sodium) functions following 30 or 45 min of IRI.
- MeSH
- akutní poškození ledvin etiologie patofyziologie prevence a kontrola MeSH
- antiflogistika nesteroidní terapeutické užití MeSH
- krysa rodu rattus MeSH
- kurkumin terapeutické užití MeSH
- potkani Wistar MeSH
- renální oběh účinky léků MeSH
- reperfuzní poškození komplikace farmakoterapie patofyziologie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Early postoperative complications after small bowel transplantation (SBT) including endotoxemia, bacterial translocations, and stimulation of the recipient's immune response have been attributed to preservation injury. Small intestine is notoriously sensitive to ischemia and there is still no general agreement as to which segment of the small bowel is preferred (jejunum or ileum) for clinical use. AIM OF STUDY: In our study, using light microscopy and concentrations of tissue serotonin-positive cells we sought to identify the part of the human intestine, which is more resistant to preservation injury sustained by HTK preservation solution with 1-24 hr cold ischemia time. RESULTS: Statistical analysis of both parameters did not reveal any significant differences between the jejunum and ileum. CONCLUSIONS: Judging by our data, there is no difference between jejunal and ileal grafts in susceptibility to ischemic injury due to cold ischemia within 24 hours when using HTK preservation solution. Significant difference was observed in histological pictures only after 12-hour of cold ischemia time in both experimental groups (jejunum and ileum).
- MeSH
- dospělí MeSH
- ileum patologie transplantace MeSH
- jejunum patologie transplantace MeSH
- lidé středního věku MeSH
- lidé MeSH
- reperfuzní poškození komplikace patologie MeSH
- senioři MeSH
- střevní sliznice patologie MeSH
- studená ischemie škodlivé účinky MeSH
- transplantace orgánů metody škodlivé účinky MeSH
- uchovávání orgánů metody škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- srovnávací studie MeSH
Vedle úmrtí nemocného je chronická transplantační nefropatie hlavní příčinou ztráty funkce transplantované ledviny v dlouhodobém sledování. Protože je v poslední desetiletí předmětem intenzivního výzkumu, názory na její příčiny se rychle vyvíjejí. Klíčovým patogenetickým momentem v rozvoji chronické transplantační nefropatie je odpověď imunitního systému na inzulin. Inzult může být způsoben akutní celulární i humorální rejekcí, které závisejí na alloantigenní bariéře. Ve stejné době se ale uplatňují i inzulity způsobené rizikovými faktory, které nezávisí na alloantigenu, jako jsou kvalita dárcovského orgánu, následky smrti mozku, ischemicko/reperfuzní postižení a faktory specifické pro příjemce (hypertenze, hyperlipidemie, infekce, léková toxicita) včetně faktorů dědičných, které ovlivňují chování imunitního systému. Následkem uvedených inzultů dochází ke kaskádě dějů, které vedou v konečném důsledku k intersticiální fibróre, tubulární atrofii a cévním změnám - typickým atributům chronické transplantační nefropatie. Prohloubení našich znalostí o patofyziologii chronické transplantační nefropatie je významné pro její adekvátní terapii, která ale bohužel zatím není příliš úspěšná.
Besides patient death, chronic allograft nephropathy remains to be the main cause of late renal allograft loss. Because of inte nsive research during last ten years, its etiopathogenesis concepts have been subjects of many changes. The response of immune system on the injury s eems to be the principle of its pathogenesis. The insult may be caused by both cellular and humoral rejections that depend on alloantigen diff erences between donor and recipient. At the same time, however, insults those are alloantigen-independent have been implicated: quality of dono r kidney, brain death injury, ischemia/reperfusion injury and recipient specific factors, such as hypertension, hyperlipidemia, infection, drug toxicity as well as genetic variants that modify the behavior of immune system. Above-mentioned insults have been involved in the pathophysiologica l mechanisms that finally result in the interstitial fibrosis, tubular atrophy and vascular lesions that morphologically characterize chroni c allograft nephropathy. Our better understanding of chronic allograft nephropathy may be im portant for future therapeutical strategies that are unsatis factory so far.
- MeSH
- chronické selhání ledvin imunologie komplikace patofyziologie MeSH
- dárci tkání klasifikace MeSH
- finanční podpora výzkumu jako téma MeSH
- hyperlipidemie genetika imunologie komplikace MeSH
- ischemie etiologie imunologie patofyziologie MeSH
- lidé MeSH
- proteinurie imunologie klasifikace komplikace MeSH
- protilátky imunologie klasifikace MeSH
- rejekce štěpu imunologie patofyziologie terapie MeSH
- reperfuzní poškození imunologie klasifikace komplikace MeSH
- rizikové faktory MeSH
- T-lymfocyty imunologie klasifikace patologie MeSH
- transplantace ledvin imunologie patologie statistika a číselné údaje MeSH
- Check Tag
- lidé MeSH
