Acute orofacial pain is associated with significant disability and has a detrimental impact on quality of life. Although various origins of the pain in trigeminal territory can be identified an odontogenic pathology is the most common cause of acute orofacial pain in patients. Due to complex pathophysiology drugs with multitarget action might provide beneficial effect in pain management. The aim of the present study was to experimentally examine the anti-nociceptive effects of tapentadol, an opioid agonist and a norepinephrine reuptake inhibitor (MOR/NRI), in our animal model of orofacial pain. We tested the effect of tapentadol at gradual doses of 1, 2 and 5 mg/kg during thermal and mechanical stimulation in the trigeminal area of adult rats. We observed that tapentadol exhibits antinociceptive effect at dosages of 2 mg/kg and 5 mg/kg and only in association with mechanical stimulation.
- MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- obličejová bolest farmakoterapie patologie MeSH
- opioidní analgetika farmakologie MeSH
- pilotní projekty MeSH
- potkani Wistar MeSH
- tapentadol farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Mental disorders affect 10-20 % of the young population in the world. Major depressive disorder (MDD) is a common mental disease with a multifactorial and not clearly explained pathophysiology. Many cases remain undetected and untreated, which influences patients' physical and mental health and their quality of life also in adulthood. The aim of our pilot study was to assess the prediction value of selected potential biomarkers, including blood cell counts, blood cell ratios, and parameters like peroxiredoxin 1 (PRDX1), tenascin C (TNC) and type IV collagen (COL4) between depressive pediatric patients and healthy peers and to evaluate a short effect of antidepressant treatment. In this study, 27 young depressive patients and 26 non-depressed age-matched controls were included. Blood analyses and immunological assays using commercial kits were performed. Platelet count was the only blood parameter for which the case/control status was statistically significant (p=0.01) in a regression model controlling for the age and gender differences. The results from ELISA analyses showed that the case/control status is a significant predictor of the parameters PRDX1 (p=0.05) and COL4 (p=0.009) in respective regression model considering the age and gender differences between MDD patients and controls. A major finding of this study is that values of platelet count, monocyte to lymphocyte ratio, white blood cell, and monocyte counts were assessed by the Random Forest machine learning algorithm as relevant predictors for discrimination between MDD patients and healthy controls with a power of prediction AUC=0.749.
- MeSH
- biologické markery analýza MeSH
- depresivní porucha unipolární diagnóza epidemiologie psychologie MeSH
- kvalita života MeSH
- lidé MeSH
- mladiství MeSH
- pilotní projekty MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
It is assumed that the Attention Deficit Hyperactivity Disorder is associated with the central autonomic dysregulation, however, the studies are rare. Analysis of pupillary light reflex represents a non-invasive tool to provide information related to the central autonomic regulation; thus, we aimed to evaluate potential disturbances in the central autonomic integrity using pupillary light reflex examination in Attention Deficit Hyperactivity Disorder. We have examined 20 children with Attention Deficit Hyperactivity Disorder (10 boys, 13.0+/-2.3 years) and 20 age/gender-matched healthy subjects. Pupillary light reflex was examined at rest for both eyes using Pupillometer PLR-2000 (NeurOptics, USA). Evaluated parameters were: diameter of the pupil before the application of light stimulus and after illumination at the peak of the constriction, the percentual change of the pupil diameter during constriction, average constriction velocity, maximum constriction velocity and average dilation velocity. We found significantly lower percentual change of the pupil diameter during constriction for both eyes in Attention Deficit Hyperactivity Disorder group compared to controls (right eye: -25.81+/-1.23 % vs. -30.32+/-1.31 %, p<0.05, left eye: -25.44+/-1.65 % vs. -30.35+/-0.98 %, p<0.05). The average constriction velocity and maximum constriction velocity were significantly shortened in left eye in Attention Deficit Hyperactivity Disorder group compared to controls (p<0.05). Our findings revealed altered pupillary light reflex indicating abnormal centrally-mediated autonomic regulation characterized by parasympathetic underactivity associated with relative sympathetic predominance in children suffering from Attention Deficit Hyperactivity Disorder.
- MeSH
- autonomní nervový systém patologie MeSH
- hyperkinetická porucha patologie MeSH
- lidé MeSH
- mladiství MeSH
- reflex pupilární fyziologie účinky záření MeSH
- studie případů a kontrol MeSH
- světelná stimulace metody MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The study examined the morphological and long-term behavioral impacts of neonatal hypoxic-ischemic brain injury in a mouse model. We investigated the modification of different behavioral domains, such as spontaneous climbing, which represents fine motor skills. We also focused on sex-dependent differences during hypoxic-ischemic encephalopathy. The Rice-Vannucci model of hypoxia-ischemia was used, adjusted and adapted to 7-day-old C57BL/6NTac mice. The effects of induced hypoxia and ischemia were also studied separately. At postnatal day 60, mice underwent behavioral testing using the LABORAS apparatus. The perfusion for histological evaluation was performed one day after the behavioral analyses. In groups with separately induced hypoxia or ischemia, the observed alterations in behavior were not accompanied by morphological changes in the cortex or hippocampal formation. Female mice naturally climbed significantly more and hypoxic females reared less than hypoxic males (p<0.05). Male mice postnatally exposed to hypoxia-ischemia exhibited significantly lower vertical activity and higher horizontal activity (p<0.05). Mild hypoxic damage may not be morphologically detectable but may induce substantial behavioral changes in adult mice. There were significant differences between horizontal and vertical activity in reaction to hypoxia-ischemia. Our study indicates that the importance of behavioral testing is irreplaceable and may be reflected in neonatal medicine.
- MeSH
- biomechanika MeSH
- chov zvířat metody MeSH
- chování zvířat * MeSH
- mozková hypoxie a ischemie patofyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- novorozená zvířata MeSH
- poranění mozku patofyziologie MeSH
- sociální izolace * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.
- MeSH
- dibutylftalát toxicita MeSH
- diethylhexylftalát toxicita MeSH
- krysa rodu rattus MeSH
- kyseliny ftalové toxicita MeSH
- matka - expozice noxám škodlivé účinky MeSH
- novorozená zvířata MeSH
- pohlavní dospělost MeSH
- pohlavní orgány účinky léků patologie MeSH
- potkani Wistar MeSH
- sociální chování * MeSH
- těhotenství MeSH
- testosteron krev MeSH
- zpožděný efekt prenatální expozice chemicky indukované patologie MeSH
- zvířata MeSH
- zvláčňovadla toxicita MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor beta (ERbeta) mRNA levels in tumor was tested. In males with low expression of ERbeta, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERbeta mRNA levels and in females. Accordingly, males with low expression of ERbeta and high expression of miR-30c showed a better survival that those with low expression ERbeta and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERbeta mRNA in tumor tissue.
- MeSH
- beta receptor estrogenů genetika metabolismus MeSH
- kohortové studie MeSH
- kolorektální nádory genetika metabolismus patologie MeSH
- lidé MeSH
- mikro RNA biosyntéza genetika MeSH
- míra přežití MeSH
- nádorové biomarkery biosyntéza genetika MeSH
- prognóza MeSH
- senioři MeSH
- sexuální faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The vagal motor fibers innervating the esophageal striated muscle are essential for esophageal motility including swallowing and vomiting. However, it is unknown which subtypes of voltage-gated sodium channels (NaV1s) regulate action potential conduction in these efferent nerve fibers. The information on the NaV1s subtypes is necessary for understanding their potential side effects on upper gut, as novel inhibitors of NaV1s are developed for treatment of pain. We used isolated superfused (35 °C) vagally-innervated mouse esophagus striated muscle preparation (mucosa removed) to measure isometric contractions of circular striated muscle evoked by electrical stimulation of the vagus nerve. NaV1 inhibitors were applied to the de-sheathed segment of the vagus nerve. Tetrodotoxin (TTX) applied to the vagus nerve completely abolished electrically evoked contractions. The selective NaV1.7 inhibitor PF-05089771 alone partially inhibited contractions and caused a >3-fold rightward shift in the TTX concentration-inhibition curve. The NaV1.1, NaV1.2 and NaV1.3 group inhibitor ICA-121431 failed to inhibit contractions, or to alter TTX concentration-inhibition curves in the absence or in the presence of PF-05089771. RT-PCR indicated lack of NaV1.4 expression in nucleus ambiguus and dorsal motor nucleus of the vagus nerve, which contain motor and preganglionic neurons projecting to the esophagus. We conclude that the action potential conduction in the vagal motor fibers to the esophageal striated muscle in the mouse is mediated by TTX-sensitive voltage gated sodium channels including NaV1.7 and most probably NaV1.6. The role of NaV1.6 is supported by ruling out other TTX-sensitive NaV1s (NaV1.1-1.4) in the NaV1.7-independent conduction.
- MeSH
- akční potenciály MeSH
- elektrická stimulace MeSH
- ezofágus inervace MeSH
- motorické neurony fyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nervus vagus fyziologie MeSH
- příčně pruhované svaly inervace MeSH
- sodíkové kanálky řízené napětím genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Obesity is characterized by chronic, low-grade systemic inflammation. Obesity may also be associated with chronic cough. The aim of this pilot study was to clarify relation of cough reflex sensitivity and body mass index (BMI) in children with chronic cough. Altogether 41 children having symptoms of chronic cough were submitted to cough reflex sensitivity measurement. We assessed the relation of cough reflex sensitivity (CKR) due to BMI. Cough reflex sensitivity was defined as the lowest capsaicin concentration which evoked two (C2) or five (C5) coughs. Capsaicin aerosol in doubling concentrations (from 0.61 to 1250 micromol/l) was inhaled by a single breath method (KoKo DigiDoser; nSpire heath Inc, Louisville, CO, USA), modified by the addition of an inspiratory flow regulator valve (RIFR; nSpire heath Inc, Louisville, CO, USA). BMI was calculated. Pulmonary function was within normal range. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children (22 boys and 19 girls, mean age 6.8 years) cough reflex sensitivity (median, with the Inter-Quartile Range) for C2 was 19.5 (73.4) micromol/l; for C5 it was 78.1 (605.5) micromol/l. We have noticed statistically significant relation of the cough reflex sensitivity (C5) and body mass index (P<0.0001); however, the effect size was small, R2=0.03. Increase of body mass index in one unit is associated with -34.959 micromol/l decrease of C5. We did not find a statistically significant relation between C2 and BMI (P=0.41). The median value of CKR (C2) in boys is not statistically significantly different than the median value of CKR (C2) in girls (P-value 0.5). The median value of CKR (C5) in boys is not statistically significantly different than the median value of CKR (C5) in girls (P-value 0.5). Increase of body mass index in children suffering from chronic cough relates to decrease of cough reflex sensitivity (C5 value).
- MeSH
- alergie patofyziologie MeSH
- chronická nemoc MeSH
- dítě MeSH
- index tělesné hmotnosti MeSH
- kapsaicin škodlivé účinky MeSH
- kašel chemicky indukované patofyziologie MeSH
- látky ovlivňující senzorický systém škodlivé účinky MeSH
- lidé MeSH
- mladiství MeSH
- pilotní projekty MeSH
- předškolní dítě MeSH
- reflex fyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Individual studies have suggested the utility of fractional exhaled nitric oxide (FeNO) measurement in detecting cough-variant asthma and eosinophilic bronchitis in patients with chronic cough. The aim of this study was to clarify a correlation of cough reflex sensitivity and fractional exhaled nitric oxide in asthmatic children. 25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement - capsaicin aerosol in doubling concentrations (from 0.61 to 1250 micromol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Fractional exhaled nitric oxide (FeNO) measurement was included. Asthmatic children' (11 boys and 14 girls, mean age 9+/-1 years) and control group (unconfirmed diagnosis of asthma) (6 boys and 9 girls, mean age 8+/-1 years) were included into the study. FeNO vs. C2 in asthma (Spearman ́s rank correlation: -0.146, p=0.49); FENO vs. C5 in asthma (Spearman ́s rank correlation: -0.777, p=0.71). We found that there is no correlation between cough reflex sensitivity and fractional exhaled nitric oxide either in children with asthma or in the control group.
- MeSH
- alergie diagnóza etiologie metabolismus MeSH
- bronchiální astma komplikace metabolismus MeSH
- dítě MeSH
- kašel diagnóza etiologie metabolismus MeSH
- lidé MeSH
- oxid dusnatý metabolismus MeSH
- reflex fyziologie MeSH
- respirační funkční testy MeSH
- ROC křivka MeSH
- vydechnutí MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases that degrades extracellular matrix (ECM) components. MMPs are associated with venous wall remodelling, proliferation, migration, phenotypic and functional transformation of vascular smooth muscle cells and ECM organization under the physiological and pathophysiological conditions. We investigated possible association of genetic promoter polymorphisms of MMP2 (rs243866), MMP8 (rs11225395), MMP9 (rs3918242) and TIMP2 (rs8179090) to varicose veins development in the Slovak population. Genomic DNA from 276 Slovak individuals (138 cases, 138 controls) was genotyped for selected SNPs (rs243866, rs11225395, rs3918242 and rs8179090) using the PCR-RFLP analysis. The data were analysed by chi-squared (chi2) test, logistic regression, and Mann-Whitney test. The risk of varicose veins development was evaluated in dominant, codominant and recessive genetic models. The statistical evaluation of selected polymorphisms in patients in all three genetic models has not shown a significant risk of varicose veins development. Our study has not shown the association between selected polymorphisms and increased risk of varicose veins development in Slovak population. More evidence with broaden sample size is needed.
- MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 genetika MeSH
- matrixová metaloproteinasa 8 genetika MeSH
- matrixová metaloproteinasa 9 genetika MeSH
- matrixové metaloproteinasy genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pilotní projekty MeSH
- promotorové oblasti (genetika) MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- tkáňový inhibitor metaloproteinasy 2 genetika MeSH
- varixy epidemiologie genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH