INTRODUCTION Vitamin D-deficiency is known to cause nerve conduction impairments, cancer and chronic diseases, as well as the pathogenesis of osteoarthritis. Our goal with this study is to evaluate the cartilage healing by applying intraarticular 1α, 25 (OH) 2D3 at different doses in rats with normal vitamin D levels and metabolism, which we made focal chondral damage model in the knee joint. MATERIAL AND METHODS 35 male Sprague-Dawley rats aged 20-24 weeks were used in our study. Both knees of rats were cartilage defected surgically on day 0. Joint injections performed at 06:00 am on 0th and 2nd days and after second injection others performed on days 9-16 and 23 following a weekly period. RESULTS In the fourth week, hematoxylin eosin staining measurements showed statistically significant difference according to the groups (p < 0.01) Metalloproteinase-13 (MMP-13) in histological staining for evaluating cartilage healing and healing levels showed statistically significant differences between the groups at first week and fourth week (p < 0.05). DISCUSSION Vitamin D, which affects many tissues through its receptors, is believed to be chondroprotective and neuroprotective by decreasing the expression of MMP in cartilage fibroblast, macrophage, lymphocyte through its intracellular receptors. To the best of our knowledge, this is the first study known to be intraarticular use of 1α, 25-dihydroxyvitamin D3. Our study has been found to be safe and successful in terms of weight, systemic PTH and 1α, 25-dihydroxyvitamin D3 levels in rats during treatment as well as better healing of cartilage damage. Key words: vitamin D3 receptor, articular cartilage, orthopedics, nerve conduction.
- MeSH
- hojení ran účinky léků MeSH
- inhibitory matrixových metaloproteinas aplikace a dávkování MeSH
- injekce intraartikulární MeSH
- kalcitriol aplikace a dávkování MeSH
- kloubní chrupavka účinky léků zranění MeSH
- krysa rodu rattus MeSH
- matrixová metaloproteinasa 13 metabolismus MeSH
- modely nemocí na zvířatech MeSH
- potkani Sprague-Dawley MeSH
- zadní končetina zranění MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF THE STUDY Septic arthritis is an infection of joints caused by a pathogenic microorganism. Septic arthritis has a mortality rate of 11-40% when it's not treated properly. The mortality rate with methicillin-sensitive Staphylococcus aureus (MSSA)is 5-7%, while the rate with methicillin-resistant Staphylococcus aureus (MRSA)is 13-20%. The aim of this study is to evaluate the effects of intraarticular vancomycin and teicoplanin on joint cartilage in in vivo settings and its utility in routine MRSA treatment. MATERIALS AND METHODS In our study, 35 male Sprague-Dawley rats aged 28 days were used. Rats were obtained from the Regenerative and Restorative Medicine Research Center (REMER) of Istanbul Medipol University. Rats were randomly divided into 5 groups each containing 7 rats. Joint injections were administered with isoflurane analgesia every day at 6 am. Three rats (15 rats) from each group were sacrified in seventh day and evaluated immunohistologically to evaluate acute healing in articular cartilage. All remaining rats were sacrificed on day 28 and their knees were evaluated by immunohistochemical examination. RESULTS In our study, there were no complications in any rat during injection and the study period. Hematoxylin eosin (H & E) histological staining for evaluating cartilage healing and healing levels did not show statistically significant differences between the groups at first week (p > 0.05). Matrix metalloproteinase-13 (MMP-13) staining did not show any statistically significant difference between the groups. (p > 0.05). DISCUSSION MRSAseptic arthritis, diagnosed for the first time in 1960, has recently been responsible for 6-22% of all septic arthritis and is increasing day by day. The use of systemic vancomycin or teicoplanin is the first-line treatment method in MRSA septic arthritis. Serum levels reach the desired level, especially with intravenous infusion dose. On the other hand, it has been shown that intraarticular concentration does not reach a sufficient level in studies conducted. The use of intraarticular antibiotics during treatment can lead to more effective and early disease control by turning this negative situation into favor of the patient. As a result, intraarticular vancomycin and teicoplanin maximale tolerable and maintenance doses can be safely used beside surgery and intravenous antibiotics to increase efficacy of treatment, reduction of recurrence rates and reduction of mortality in MRSAseptic arthritis. CONCLUSIONS Intraarticular vancomycin and teicoplanin maximale tolerable and maintenance doses can be safely used beside surgery and intravenous antibiotics to increase efficacy of treatment, reduction of recurrence rates and reduction of mortality in MRSA septic arthritis. Key words:arthritis, infectious; methicillin-resistant Staphylococcus aureus; mortality.
- MeSH
- antibakteriální látky aplikace a dávkování MeSH
- hojení ran účinky léků MeSH
- infekční artritida farmakoterapie patologie MeSH
- injekce intraartikulární MeSH
- kloubní chrupavka účinky léků patologie MeSH
- krysa rodu rattus MeSH
- methicilin rezistentní Staphylococcus aureus izolace a purifikace MeSH
- modely nemocí na zvířatech MeSH
- náhodné rozdělení MeSH
- potkani Sprague-Dawley MeSH
- stafylokokové infekce farmakoterapie patologie MeSH
- teikoplanin aplikace a dávkování MeSH
- vankomycin aplikace a dávkování MeSH
- zadní končetina účinky léků mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
Cíl: Neuroprotektivní účinky klopidogrelu již byly prokázány na různých experimentálních modelech. Vzhledem k tomu, že klopidogrel je dobře tolerován a schválen k používání v různých klinických podmínkách, může být atraktivním kandidátem pro další klinická zkoumání, zejména v situaci, kdy se antiedematický účinek jeví jako vhodná adjuvantní strategie, například při poranění mozku. Naším záměrem bylo prozkoumat neuroprotektivní roli klopidogrelu při poranění mozku. Metody: Pro zkoumání účinků klopidogrelu jsme navodili poranění mozku s použitím modelu chladového traumatu u myší a zkoumali jsme základní mechanizmus přežití/ odumírání buněk s použitím kresolové violeti, barvení TUNEL a analýzy western blot. Výsledky: Klopidogrel v dávce 3 mg/ kg vedl k signifikantnímu snížení otoku mozku. Podobný pokles byl pozorován při dávce klopidogrelu 10 mg/ kg a 30 mg/ kg. Rovněž jsme prokázali, že klopidogrel blokoval prominentní cesty poškození zánětem a vykazoval silný antiaptotický účinek (3 a 30 mg/ kg), který byl spojen se zvýšenou možností přežití neuronových buněk. Klopidogrel (3, 10 a 30 mg/ kg) měnil dávkově dependentním způsobem hladiny JNK, p-38, AKT, ERK a p53. Závěr: Naše nálezy prokazují, že klopidogrel může být novým kandidátem pro zmírnění posttraumatického poranění mozku a edému. Domníváme se, že může být aplikován hlavně v akutních fázích cerebrální ischemie, která je charakterizována hemoragickou transformací a edémem mozku.
Aim: The neuroprotective effects of clopidogrel have already been shown in various experimental models. Taking into account the fact that clopidogrel is well tolerated and approved for use in various clinical settings, it can be an attractive candidate for further clinical investigations, especially when the anti-oedema effect appears to be a reasonable adjuvant strategy, such as in brain injury (BI). Here we aimed to examine the neuroprotective role of clopidogrel in BI. Methods: To investigate the effects of clopidogrel, we induced BI in mice using a cold trauma model and evaluated the underlying cell survival/ death mechanisms via cresyl violet, TUNEL staining and western blot analysis. Results: Clopidogrel at a dose of 3 mg/ kg led to a significant reduction in brain swelling. Similar decreases were observed with 10 mg/ kg and 30 mg/ kg of clopidogrel. We also have shown that clopidogrel blocks the prominent inflammatory injury pathways and exerts a significant anti-apoptotic effect (3 and 30 mg/ kg), which has been associated with increased neuronal cell survival pathways. Clopidogrel (3, 10 and 30 mg/ kg) dose-dependently altered the JNK, p-38, AKT, ERK and p53 levels. Conclusion: Our findings demonstrate that clopidogrel can be a novel candidate for the reduction of post-traumatic BI and oedema. We propose that it can be applied mainly in the acute phases of cerebral ischaemia, which is characterized by haemorrhagic transformation and brain oedema.
- Publikační typ
- abstrakt z konference MeSH