The two i nferior colliculi (IC) are paired structures in the midbrain that are connected to each other by a bundle of commissural fibers. The fibers play an important role in coordinating sound signal processing between the two inferior colliculi. This study examined inter-collicular suppression on sound signal processing in amp litude domain of mice by measuring the rate-amplitude functions (RAFs) of neurons in one IC during the electrical stimulation of the opposite IC. Three types (monotonic, saturated and non-monotonic) RAFs of collicular neurons were measured before and durin g inter-collicular suppression. Inter-collicular suppression significantly increased the slope, decreased the dynamic range and narrowed down the responsive amplitude of all RAFs to high amplitude level but did not change the type of most (36/43, 84 % ) RAFs. As a result, all types of RAFs were compressed at a greater degree at low than at high sound amplitude during inter-collicular suppression. These data indicate that inter-collicular suppression improve sound processing in the high amplitude domain., Liang Cheng, Hui-Xian Mei, Yun Huang., and Obsahuje bibliografii
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., A. Khodorova, Y. Zhang, G. Nicol, G. Strichartz., and Seznam literatury
ntestinal inflammation induced with dextran sodium sulfate (DSS) is used to study acute or chronic ulcerative colitis in animal models. Decreased gut tissue anti-inflammatory cytokine IL-10 concentration and mRNA abundance are associated with the development of chronic bowel inflammation. Twelve piglets of 3 days old were fitted with an intragastric catheter and randomly allocated into control and DSS groups by administrating either sterile saline or 1.25 g of DSS/ kg body weight (BW) in saline per day, respectively, for 10 days. Growth rate and food conversion efficiency were reduced (p<0.05) in the DSS piglets compared with the control group. Quantitative histopathological grading of inflammation in the jejunum and colon collectively showed that the DSS tr eatment resulted in 12 fold greater (p<0.05) inflammation severity scoring in the colon than in the jejunum, indicative of chronic ulcerative colitis in the colon. Upper gut permeability endpoint was 27.4 fold high er (p<0.05) in the DSS group compared with the control group. The DSS group had higher concentrations and mRNA abundances (p<0.05) of TNF - α and IL-6 in the jejunal and colonic tissues compared with the control group. Colonic concentration and mRNA abundanc e of IL-10 were reduced (p<0.05), however, jejunal IL-10 mRNA abundance was increased (p<0.05) in the DSS group compared with the control group. In conclusion , administration of DSS at 1.25 g/kg BW for 10 days respectively induced acute inflammation in th e jejunum and chronic inflammation and ulcerative colitis in the colon with substantially decreased colonic concentration and mRNA abundance of IL-10 in the young pigs, mimicking the IL-10 expression pattern in humans associated with chronic bowel inflamma tion., D. Lackeyram, D. Young, C. J. Kim, C. Yang, T. L. Archbold, Y. Mine, M. Z. Fan., and Obsahuje bibliografii
Nanocarriers bearing anticancer drugs are promising candidates to improve the efficacy of cancer therapy and minimize side effects. The most potent cytostatics used in the treatment of various cancers are anthracyclines, e.g. doxorubicin or pirarubicin. Recently, polymer therapeutics carrying anthracyclines have been intensively studied. The precise characterization of in vitro nanocarrier biological behavior brings a better understanding of the nanocarrier characteristics and enables prediction of the behavior of the nanocarrier during in vivo application. Advanced fluorescence detection methods, e.g. fluorescence lifetime imaging microscopy (FLIM), were successfully exploited to describe the properties of various polymeric nano-systems and contributed to a complex view of anthracyclines’ intracellular transport and DNA intercalation. Here, we report the application of a specific technique for processing FLIM images, called fluorescence pattern decomposition, to evaluate early events after doxorubicin or pirarubicin treatment of cells. Moreover, we characterized changes in the intracellular localization and release of the anthracyclines during the incubation of cells with polymer nanotherapeutics based on poly[N-(2-hydroxypropyl)- methacrylamide] (pHPMA)., J. Panek, E. Koziolova, P. Stepanek, T. Etrych, O. Janouskova., and Obsahuje bibliografii
The skeleton shows an unconventional role in the physiology and pathophysiology of the human organism, not only as the target tissue for a number of systemic hormones, but also as endocrine tissue modulating some skeletal and extraskeletal systems. From this point of view, the principal cells in the skeleton are osteocytes. These cells primarily work as mechano-sensors and modulate bone remodeling. Mechanically unloaded osteocytes synthetize sclerostin, the strong inhibitor of bone formation and RANKL, the strong activator of bone resorption. Osteocytes also express hormonally active vitamin D (1,25(OH)2D) and phosphatonins, such as FGF23. Both 1,25(OH)2D and FGF23 have been identified as powerful regulators of the phosphate metabolism, including in chronic kidney disease. Further endocrine cells of the skeleton involved in bone remodeling are osteoblasts. While FGF23 targets the kidney and parathyroid glands to control metabolism of vitamin D and phosphates, osteoblasts express osteocalcin, which through GPRC6A receptors modulates beta cells of the pancreatic islets, muscle, adipose tissue, brain and testes. This article reviews some knowledge concerning the interaction between the bone hormonal network and phosphate or energy homeostasis and/or male reproduction., I. Zofkova., and Obsahuje bibliografii
Here we studied whether descending control of mechanical nociception by glutamate in the central nucleus of the amygdala (CeA) of healthy control animals is induced by amygdaloid NMDA receptors and relayed through the midbrain periaqueductal gray (PAG). Mechanical nociception in the hind paws was assessed in rats with chronic guide cannulae for glutamate administration in the right CeA and for inducing local anesthesia in the PAG. In a separate electrophysiological study, ON-like PAG neurons giving an excitatory response to noxious pinch of the tail were recorded in anesthetized rats following glutamate administration into the CeA. A high dose of glutamate (100 μg) in the CeA induced mechanical antinociception in the contra- but not ipsilateral hind limb. Antinociception was prevented by an NMDA receptor antagonist in the CeA or local anesthesia of the PAG. Discharge rate of ON-like PAG neurons was increased by a high dose of glutamate (100 μg) in the CeA and this increase was prevented by an NMDA receptor antagonist in the CeA. The results indicate that amygdaloid NMDA receptors in the CeA may induce contralaterally mechanical antinociception through a circuitry relaying in the PAG. Activation of ON-like PAG neurons is associated with the descending antinociceptive effect. Mechanisms and causality of this association still remain to be studied., N. Bourbia, A. Pertovaara., and Obsahuje bibliografii
Iodine is essential in the biosynthesis of thyroid hormones that affect metabolic processes in the organism from the prenatal state to the elderly. The immediate indicator of iodine intake is the concentration of iodine in urine, but the indicator of iodine intake in the longer term of several months is thyroglobulin (Tg). Tg negatively correlated with increasing intake of iodine in population that do not suffer from thyroid disease, while a more than adequate to excessive iodine intake leads to an increase in Tg. The dependence of Tg on iodine can be described by a U-shaped curve. Thyroglobulin in serum is elevated in thyroid disease mainly in hyperthyroidism (diagnosis E05 of WHO ICD-10 codes) and in goiter (diagnosis E04 of WHO ICD-10 codes). Tg values decrease below 20 µg/l after effective treatment of patients with thyroid disease. Thyroglobulin may thus be an indicator of thyroid stabilization and the success of the thyroid gland treatment., Radovan Bílek, Marcela Dvořáková, Tereza Grimmichová, Jan Jiskra., and Obsahuje bibliografii
Interesting and stimulating data about the effect of the perivascular adipose tissue size on atherogenesis are based mainly on CT findings. We studied this topic by directly analyzing perivascular adipose tissue in explanted hearts from patients undergoing transplantation. Ninety -six consecutive patients were included, including 58 with atherosclerotic coronary heart disease (CHD) and 38 with dilation cardiomyo pathy (DCMP). The area of perivascular fat, area of the coronary artery wall, and ratio of CD68 -positive macrophages within the perivascular fat and within the vascular wall were quantified by immunohistochemistry. There was no significant difference in th e perivascular adipose tissue size between the two groups. Nevertheless, there was a significantly higher number of macrophages in the coronary arterial wall of CHD patients. In addition, we found a close relationship between the ratio of macrophages in th e arterial wall and adjacent perivascular adipose tissue in the CHD group, but not in the DCMP group . According to our data interaction between macrophages in the arterial wall and macrophages in surrounding adipose tissue could be more important mechanism of atherogenesis than the size of this tissue itself., I. Kralova Lesna, Z. Tonar, I. Malek, J. Maluskova, L. Nedorost, J. Pirk, J. Pitha, V. Lanska, R. Poledne., and Obsahuje bibliografii
The name of Jan Evangelista Purkyně and the cerebellum belong inseparably together. He was the first who saw and described the largest nerve cells in the brain, de facto in the cerebellum. The most distinguished researchers of the nervous system then showed him the highest recognition by naming these neurons as Purkinje cells. Through experiments by J. E. Purkyně and his followers properly functionally was attributed to the cerebellum share in precision of motor skills. Despite ongoing and fruitful research, after a relatively long time, especially in the last two decades, scientists had to constantly replenish and re-evaluate the traditional conception of the cerebellum and formulate a new one. It started in the early 1990s, when it was found that cerebellar cortex contains more neurons than the cerebral cortex. Shortly thereafter it was gradually revealed that such enormous numbers of neural cells are not without an impact on brain functions and that the cerebellum, except its traditional role in the motor skills, also participates in higher nervous activity. These new findings were obtained thanks to the introduction of modern methods of examination into the clinical praxis, and experimental procedures using animal models of cerebellar disorders described below., F. Vožeh., and Obsahuje bibliografii