Úvod a cíl: Nový typ koronaviru (COVID-19) způsobuje vysokou horečku, únavu, kašel, dechové potíže, průjmy, u některých pacientů bolesti hlavy, cerebrovaskulární onemocnění, bezvědomí, encefalopatii, encefalitidu, poškození periferního nervového systému atd. Jedná se o virové respirační onemocnění, které se projevuje neurologickými nálezy. V naší studii byly zkoumány hladiny neurotrofického faktoru odvozeného od glií (glial-derived neurotrophic factor; GDNF) a nervového růstového faktoru (nerve growth factor; NGF) neurotrofických faktorů (NF), které zajišťují přežití, růst, zrání a diferenciaci neuronů u pacientů s COVID-19 a jejich vztah se závažností onemocnění. Materiál a metody: Z celkového počtu 70 účastníků je 20 účastníků ve zdravé kontrolní skupině (CG) a 50 účastníků je ve skupině pacientů s COVID-19 dle PCR testu (nekomplikovaná skupina [NCG], středně těžká skupina [MG], těžká skupina [SG]). Hladiny NGF a GDNF v séru ve všech skupinách byly hodnoceny spektrofotometricky pomocí metody ELISA. Výsledky byly porovnány jak mezi skupinami pacientů, tak mezi pacienty a kontrolní (zdravou) skupinou. Výsledky: Koncentrace NGF v séru byla signifikantně vyšší ve skupině MG než ve skupinách NCG a SG (p = 0,042). U sérových hladin GDNF u pacientů s COVID-19 a CG nebyly zjištěny statisticky významné rozdíly. Závěr: Nebyl zjištěn žádný rozdíl v sérových hladinách NGF a sérových hladinách GDNF u pacientů s onemocněním COVID-19 ve srovnání se zdravou kontrolní skupinou.
Introduction and objective: The new type of coronavirus (COVID-19) causes high fever, fatigue, cough, respiratory distress, diarrhea, headache in some patients, cerebrovascular diseases, unconsciousness, encephalopathy, encephalitis, peripheral nervous system damage, etc. It is a viral respiratory disease that manifests itself with neurological findings. In our study, glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) levels of neurotrophic factors (NF), which ensure the survival, growth, maturation and differentiation of neurons were investigated in COVID-19 patients, including their relationship with the severity of the disease. Materials and methods: Out of a total of 70 participants, 20 participants are in the healthy control group (CG) and 50 participants are in the group of patients with COVID-19 according to PCR test (uncomplicated group [NCG], moderately severe group [MG], severe group [SG]). Serum NGF and GDNF levels in all groups were evaluated spectrophotometrically using ELISA kits. The results were compared both between the patient groups and between the patient and healthy control groups. Results: Serum NGF concentration was significantly higher in the MG group than in the NCG and the SG group (P = 0.042). No statistically significant difference was found in serum GDNF levels in COVID-19 patients and CG. Conclusion: There was no difference in serum NGF and serum GDNF levels in COVID-19 patients compared to the healthy control group.
- Klíčová slova
- neurotrofický faktor odvozený od gliových buněk,
- MeSH
- COVID-19 * patofyziologie MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- nervový růstový faktor analýza MeSH
- Check Tag
- lidé MeSH
AIMS: By measuring the extent of cytokines secreted by human dental pulp stem cells (hDPSCs) from passages 2 through 10, the optimal passage of hDPSCs was determined. This offers a potential theoretical basis for the treatment of neurological disorders. METHOD: After isolation and culture of hDPSCs from human teeth, the morphological features of the cells were observed under an inverted microscope. hDPSCs were identified by their immunophenotypes and their multiple differentiation capability. Cytokine concentrations secreted in the supernatants at passages 2-10 were detected by ELISA. RESULTS: hDPSCs were viewed as fusiform or polygonal in shape, with a bulging cell body, homogenized cytoplasm, and a clear nucleus. Moreover, they could differentiate into neuroblasts in vitro. hDPSCs at passage 3 were positive for CD29 (91.5%), CD73 (94.8%) and CD90 (96.7%), but negative for the hematopoietic markers CD34 (0.13%). ELISA results showed that hDPSCs at passage 3 had the highest secretion levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), with the highest secretion level of Neurotrophin-3 (NT-3) being at passage 2. CONCLUSION: hDPSCs have steady biological features of stem cells and exhibit optimal proliferation potential. hDPSCs at different passages have different capacities in the secretion of VEGF, BDNF, NGF, and NT-3. In conclusion cytokines secreted by hDPSCs may prove to be appropriate in the treatment of neurological diseases.
- MeSH
- buněčná diferenciace * MeSH
- cytokiny * metabolismus MeSH
- kmenové buňky * metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- nervový růstový faktor metabolismus MeSH
- neurotrofin 3 metabolismus MeSH
- proliferace buněk MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zubní dřeň cytologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Důležitou roli při přenosu informace z místa poškození do mozku hraje nervový růstový faktor. Jedná se o neurotrofin modulující bolest a citlivost, který je produkován různými typy buněk a zároveň je jeho tvorba indukována prozánětlivými cytokiny. Tanezumab je humanizovaná monoklonální protilátka selektivně se vázající na nadbytečný nervový růstový faktor, a tím blokující přenos bolesti. Účinek byl prokázán v preklinické fázi na modelech pro bolest spojenou s osteoartrózou, bolest bederní páteře i bolest u nádorových onemocnění. Článek seznamuje s výsledky posledních klinických studií, které byly provedeny po odvolání dočasného pozastavení klinického výzkumu ze strany amerického Úřadu pro kontrolu potravin a léčiv. Po obnovení klinických studií bylo změněno podání tamezumabu intravenózního na subkutánní, jeho indikace se zaměřila na pacienty se selháním běžné analgetické medikace a ve všech studiích byla důsledně hodnocena kloubní bezpečnost.
Nerve growth factor plays an important role in the transmission of information from the site of injury to the brain. It is a neurotrophin that modulates pain and tenderness, which is produced by various cell types and at the same time its production is induced by proinflammatory cytokines. Tanezumab is a humanized monoclonal antibody that selectively binds to excess nerve growth factor, thereby blocking pain transmission. The effect was demonstrated in the preclinical phase in models for pain associated with osteoarthritis, lumbar spine pain and cancer pain. The article introduces the results of recent clinical trials conducted following the revocation of the temporary suspension of clinical research by the US Food and Drug Administration. Following the resumption of clinical trials, intravenous tanezumab was changed to subcutaneous, the indication was targeted to patients with failure of standard analgesic medication, and joint safety was rigorously evaluated in all studies.
- Klíčová slova
- tanezumab, fasinumab,
- MeSH
- analgetika aplikace a dávkování farmakologie MeSH
- bolest farmakoterapie patofyziologie MeSH
- humanizované monoklonální protilátky aplikace a dávkování farmakologie MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé MeSH
- management bolesti * metody statistika a číselné údaje trendy MeSH
- multicentrické studie jako téma MeSH
- nervový růstový faktor antagonisté a inhibitory fyziologie MeSH
- neurotrofní faktory agonisté klasifikace MeSH
- osteoartróza * farmakoterapie MeSH
- randomizované kontrolované studie jako téma MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
Dose-limiting nephrotoxicity restricts Cisplatin use in high therapeutic doses. Empagliflozin showed a reno-protective effect in diabetic nephropathy. We investigated if Empagliflozin can ameliorate Cisplatin nephrotoxicity whether used prophylactically or therapeutically. Forty male Wistar rats were divided into 5 groups: (1) control; (2) Cisplatin-induced nephrotoxicity by single intraperitoneal dose; (3) Empagliflozin was given for 10 days before a single dose of Cisplatin; (4) a single dose of Cisplatin followed by Empagliflozin for 10 days; (5) received Empagliflozin only. Regular assessment of weight was done, biochemical evaluation for serum urea, creatinine, uric acid, albumin, and glucose was performed, kidney tissue nerve growth factor-β (NGF-β) and oxidative stress parameters were measured, kidneys were evaluated histopathologically and immunostained for caspase 3. Cisplatin significantly reduced body weight, NGF-β, and reduced glutathione, elevated urea, creatinine, and malondialdehyde with no effect on other serum biochemical parameters. Histopathologically, there was high acute tubular necrosis (ATN) score with strong immunostaining of caspase 3. The use of Empagliflozin significantly reduced urea and creatinine in both prophylactic and therapeutic, reduced ATN score in the prophylactic group associated with minimal staining of caspase 3 and elevated reduced glutathione. In conclusion, prophylactic Empagliflozin protected against Cisplatin-induced acute kidney injury mainly via anti-apoptotic effect.
- Klíčová slova
- Empagliflozin,
- MeSH
- akutní poškození ledvin chemicky indukované krev patologie prevence a kontrola MeSH
- antitumorózní látky MeSH
- cisplatina * aplikace a dávkování farmakologie škodlivé účinky MeSH
- diabetické nefropatie farmakoterapie prevence a kontrola MeSH
- glifloziny * aplikace a dávkování farmakologie metabolismus MeSH
- glutathion analýza MeSH
- hypoglykemika MeSH
- kaspasa 3 biosyntéza účinky léků MeSH
- ledviny patologie účinky léků MeSH
- malondialdehyd analýza MeSH
- modely nemocí na zvířatech MeSH
- nádory farmakoterapie MeSH
- nervový růstový faktor analýza účinky léků MeSH
- nežádoucí účinky léčiv MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
V článku je uveden přehled poznatků o úloze nervového růstového faktoru (NGF – nerve growth factor) v mechanismech nocicepce a jeho biochemických a fyziologických vazeb na periferní a centrální úrovni. Z těchto patofyziologických poznatků vyplynula syntéza tanezumabu jako vysoce selektivní IgGZ A monoklonální protilátky selektivně vázající nervový růstový faktor, kterou je možné použít k léčení bolestivých stavů při jeho zvýšení.
In this article is described the survey of the findings of the role of nerve growth factor (NGF)in the mechanism of nicieption and it ́s biochemical and physiological processes on the peripheral and central level. These pathophysiological findings serve as a background for the construction of tanezumab as a hight selective IgGZA and monoclonal antidote chemicaly binding NGF nerve growth factor, wich is the possible the use for treatment especially of the chronic pain, caused by its increasing. of NGF.
- MeSH
- bolest * farmakoterapie MeSH
- chronická bolest farmakoterapie MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- lidé MeSH
- nádory patofyziologie MeSH
- nervový růstový faktor * antagonisté a inhibitory fyziologie škodlivé účinky MeSH
- nezvladatelná bolest farmakoterapie MeSH
- periferní nervový systém fyziologie účinky léků MeSH
- regenerace nervu MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Endothelin-1 (ET-1) and Nerve Growth Factor (NGF) are proteins, released from cancer-ridden tissues, which cause spontaneous pain and hypersensitivity to noxious stimuli. Here we examined the electrophysiological and behavioral effects of these two agents for evidence of their interactions. Individual small-medium cultured DRG sensory neurons responded to both ET-1 (50 nM, n=6) and NGF (100 ng/ml, n=4), with increased numbers of action potentials and decreased slow K(+) currents; pre-exposure to ET-1 potentiated NGF´s actions, but not vice versa. Behaviorally, single intraplantar (i.pl.) injection of low doses of ET-1 (20 pmol) or NGF (100 ng), did not increase hindpaw tactile or thermal sensitivity, but their simultaneous injections sensitized the paw to both modalities. Daily i.pl. injections of low ET-1 doses in male rats caused tactile sensitization after 21 days, and enabled further tactile and thermal sensitization from low dose NGF, in ipsilateral and contralateral hindpaws. Single injections of 100 ng NGF, without changing the paw's tactile sensitivity by itself, acutely sensitized the ipsilateral paw to subsequent injections of low ET-1. The sensitization from repeated low ET-1 dosing and the cross-sensitization between NGF and ET-1 were both significantly greater in female than in male rats. These findings reveal a synergistic interaction between cutaneously administered low doses of NGF and ET-1, which could contribute to cancer-related pain.
- MeSH
- bolest chemicky indukované metabolismus MeSH
- endotelin-1 aplikace a dávkování metabolismus toxicita MeSH
- fyzikální stimulace škodlivé účinky MeSH
- hmat účinky léků fyziologie MeSH
- injekce subkutánní MeSH
- krysa rodu rattus MeSH
- měření bolesti metody MeSH
- nervový růstový faktor aplikace a dávkování metabolismus toxicita MeSH
- potkani Sprague-Dawley MeSH
- vazba proteinů fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Neurotrophins are present in the gastrointestinal tract where they participate in the survival and growth of enteric neurons, augmentation of enteric circuits, elevation of colonic myoelectrical activity and also in different aspects of colitis. Previous studies largely focused on the role of neural and mucosal neurotrophins in gut inflammation. The expression of neurotrophins in colonic smooth muscle cells (SMCs) and the interactions of this potential source with colitis has not been studied in the gut. The expression of NGF, BDNF, NT-3 and NT-4 in SMCs from longitudinal and circular muscle layers of rat colon from normal and dextran sodium sulphate (DSS)-induced colitis rats was measured by ELISA. NGF, BDNF, NT-3 and NT-4 are differentially expressed in both longitudinal and circular SMCs, where the expressions of BDNF and NT-4 proteins were greater in SMCs from the longitudinal muscle layer than from the circular muscle layer, while NGF protein expression was greater in circular SMCs and NT-3 expression was equal in cells from both muscle layers. Induction of colitis with DSS significantly alters neurotrophins expression pattern in colonic SMCs. NGF levels upregulated in circular SMCs. BDNF level was increased in DSS-induced colitis in longitudinal SMCs. NGF, NT-3 and NT-4 levels were downregulated in longitudinal SMCs of DSS-induced colitis rats' colon. Disturbances of neurotrophins expression in SMCs resulted from colitis might account for the structural and functional changes in inflammatory bowel disease (IBD) such as loss of innervation and characteristic hypercontractility of longitudinal muscle in IBD.
- MeSH
- hladké svalstvo metabolismus patologie MeSH
- kolitida chemicky indukované metabolismus patologie MeSH
- kolon metabolismus patologie MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- myocyty hladké svaloviny metabolismus patologie MeSH
- nervový růstový faktor metabolismus MeSH
- neurotrofin 3 metabolismus MeSH
- neurotrofní faktory metabolismus MeSH
- potkani Sprague-Dawley MeSH
- síran dextranu * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
We aimed to determine whether 10 days of treadmill exercise can increase skeletal muscle mass and intramuscular concentrations of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in experimental autoimmune encephalomyelitis (EAE). Forty female Lewis rats were randomly assigned to either EAE sedentary (EAE-Sed), EAE exercise (EAE-Ex), Control sedentary (Con-Sed) and Control exercise (Con-Ex). Exercising animals completed a 10 day forced exercising training program. Hind limb skeletal muscles were excised and weighed with soleus muscle used for BDNF and NGF quantification. Statistical analysis was done using a one-way analysis of variance. Disability was more pronounced in the EAE-Ex group than in the EAE-Sed group. Exercising animals (EAE-Ex and Con-Ex) had significantly greater bilateral EDL, plantaris and gastrocnemius muscle mass compared to their sedentary animals (p=0.01). The EAE-Ex group had significantly higher NGF concentrations (1.98+/-0.3 pg/mg) compared to Con-Ex (0.96+/-0.07 pg/mg, p=0.003) and Con-Sed (1.2+/-0.2 pg/mg, p=0.04) groups. The main effect of exercise represented a significantly lower BDNF concentrations in the soleus of exercising animals compared to sedentary animals (p=0.03). Our study provides preliminary evidence that exercise increases skeletal muscle mass despite the early onset of disability in EAE animals.
- MeSH
- encefalomyelitida autoimunitní experimentální patologie terapie MeSH
- kondiční příprava zvířat metody MeSH
- kosterní svaly růst a vývoj patologie MeSH
- krysa rodu rattus MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- nervový růstový faktor metabolismus MeSH
- posuzování pracovní neschopnosti MeSH
- potkani inbrední LEW MeSH
- sedavý životní styl MeSH
- tělesná hmotnost MeSH
- terapie cvičením metody MeSH
- zadní končetina patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The ontogenetic period of life and stress can have different effects on the nerve growth factor (NGF) in the hypothalamus. The aim of our study was to investigate the influence of two mild stressors, acute and chronic exposure to forced swim (FS) or high-light open field (HL-OF), on neurons containing NGF. Immunofluorescence staining was used to reveal the density of NGF-immunoreactive (ir) cells in the hypothalamic supraoptic nucleus (SON) in adult (postnatal day 90; P90) and aged (P720) rats. The P90 and P720 rats that were subjected to acute and chronic FS showed no differences in the density of NGF-ir neurons in the SON compared with nonstressed rats. However, a significant increase in NGF-ir cells was noted after acute but not after chronic HL-OF only in P90 rats. What is more, there were no age-related (P90 vs. P720) changes in the density of NGF-ir neurons in non-stressed and FS- or HL-OF-stressed rats. Our results indicate that acute HL-OF was the only factor inducing changes in the density of NGF-ir neurons in the SON of adult rats. This could be related to the neuroprotective role of NGF-ir cells in response to acute HL-OF. The absence of age-dependent changes in the density of NGF-ir neurons may indicate that the ageing processes in SON do not generate changes in the NGF immunoreactivity of its neurons.
- MeSH
- imunohistochemie metody MeSH
- nervový růstový faktor metabolismus MeSH
- neurony metabolismus patologie MeSH
- nucleus supraopticus metabolismus patologie MeSH
- plavání MeSH
- počet buněk MeSH
- potkani Wistar MeSH
- psychický stres metabolismus MeSH
- stárnutí metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Brain development is determined by neuronal differentiation including changes of cell polarity and asymetric grow- th of neuronal processes. Although, there are many unkown factors contributing to changes of lenght of neuronal cones, mounting experimental and review papers focus on changes of growth conus and role of axonal transport. In particular, mechanisms of actin/microtubule polymerisation and depolymerisation are important. Role of intracellu- lar calcium is also significant. Normal and properly timed changes of lenght of axons and dendrites are dependent on interaction of neurons and glia. Moreover, regeneration of injured axons is dependent on growth factors secre- ted from glial cells. The aim of the present study is characterisation of the most important mechanisms underlying changes of lenght of neurites.
- Klíčová slova
- kofilin,
- MeSH
- aktiny biosyntéza MeSH
- axony fyziologie MeSH
- dendrity fyziologie MeSH
- dyneiny biosyntéza fyziologie MeSH
- lidé MeSH
- mikrotubuly fyziologie MeSH
- morfogeneze MeSH
- mozková kůra růst a vývoj MeSH
- myosiny biosyntéza fyziologie MeSH
- nervový růstový faktor MeSH
- nervový systém - fyziologické jevy MeSH
- neurity MeSH
- neuroglie cytologie MeSH
- neurony fyziologie MeSH
- růst MeSH
- synapse MeSH
- vápník zásobování a distribuce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH