Motoneuron firing properties are modified by trans-spinal direct current stimulation in rats.

Spinal polarization evoked by direct current stimulation [trans-spinal direct current stimulation (tsDCS)] is a novel method for altering spinal network excitability; however, it remains not well understood. The aim of this study was to determine whether tsDCS influences spinal motoneuron activity. Twenty Wistar rats under general pentobarbital anesthesia were subjected to 15 min anodal (n = 10) or cathodal (n = 10) tsDCS of 0.1 mA intensity, and the electrophysiological properties of their motoneurons were intracellularly measured before, during, and after direct current application. The major effects of anodal intervention included increased minimum firing frequency and the slope of the frequency-current (f-I) relationship, as well as decreased rheobase and currents evoking steady-state firing (SSF). The effects of cathodal polarization included decreased maximum SSF frequency, decreased f-I slope, and decreased current evoking the maximum SSF. Notably, the majority of observed effects appeared immediately after the current onset, developed during polarization, and outlasted it for at least 15 min. Moreover, the effects of anodal polarization were generally more pronounced and uniform than those evoked by cathodal polarization. Our study is the first to present polarity-dependent, long-lasting changes in spinal motoneuron firing following tsDCS, which may aid in the development of more safe and accurate application protocols in medicine and sport. NEW & NOTEWORTHY Trans-spinal direct current stimulation induces significant polarity-dependent, long-lasting changes in the threshold and firing properties of spinal motoneurons. Anodal polarization potentiates motoneuron firing whereas cathodal polarization acts mainly toward firing inhibition. The alterations in rheobase and rhythmic firing properties are not restricted to the period of current application and can be observed long after the current offset.

Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis.

PURPOSE: The biological association between chronic lymphocytic thyroiditis (CLT) and differentiated thyroid cancer (DTC) has not been elucidated yet. The aim of the study was to assess whether the presence of CLT exerts any influence on clinical or histological presentation of DTC. METHODS: Nine hundred and seven consecutive patients with DTC treated in the years 1998-2016 were divided into two groups according to the presence or absence of concomitant CLT. The statistical differences were analysed. RESULTS: Out of 907 patients included in the study, 331 were diagnosed with DTC and CLT (studied group), while 576 patients with DTC but without CLT constituted a control group. The distribution of papillary and follicular thyroid cancer did not differ. In CLT group, the prevalence of pT1 was greater than for pT2-pT4 DTC (P = 0.0003; OR = 1.69, 95% CI 1.27-2.24) compared to controls (68.3 vs. 56.1%, respectively). The presence of multifocal lesions was similar. The thyroid capsule infiltration without extrathyroidal invasion (P < 0.0001; OR = 0.21, 95% CI 0.14-0.31) was more frequent in the studied group, unlike extracapsular invasion, which was significantly more often present in patients with DTC but without CLT (P = 0.004; OR = 1.66; 95% CI 1.17-2.34) as well as nodal involvement (P = 0.048; OR = 0.65, 95% CI 0.42-0.99). CONCLUSIONS: The collected data indicate a protective role of CLT in preventing the spread of the DTC. The presence of CLT might limit tumour growth to the primary site.

Long-term effects of direct current are reproduced by intermittent depolarization of myelinated nerve fibers.

Direct current (DC) potently increases the excitability of myelinated afferent fibers in the dorsal columns, both during DC polarization of these fibers and during a considerable (>1 h) postpolarization period. The aim of the present study was to investigate whether similarly long-lasting changes in the excitability of myelinated nerve fibers in the dorsal columns may be evoked by field potentials following stimulation of peripheral afferents and by subthreshold epidurally applied current pulses. The experiments were performed in deeply anesthetized rats. The effects were monitored by changes in nerve volleys evoked in epidurally stimulated hindlimb afferents and in the synaptic actions of these afferents. Both were found to be facilitated during as well as following stimulation of a skin nerve and during as well as following epidurally applied current pulses of 5- to 10-ms duration. The facilitation occurring ≤2 min after skin nerve stimulation could be linked to both primary afferent depolarization and large dorsal horn field potentials, whereas the subsequent changes (up to 1 h) were attributable to effects of the field potentials. The findings lead to the conclusion that the modulation of spinal activity evoked by DC does not require long-lasting polarization and that relatively short current pulses and intrinsic field potentials may contribute to plasticity in spinal activity. These results suggest the possibility of enhancing the effects of epidural stimulation in human subjects by combining it with polarizing current pulses and peripheral afferent stimulation and not only with continuous DC. NEW & NOTEWORTHY The aim of this study was to define conditions under which a long-term increase is evoked in the excitability of myelinated nerve fibers. The results demonstrate that a potent and long-lasting increase in the excitability of afferent fibers traversing the dorsal columns may be induced by synaptically evoked intrinsic field as well as by epidurally applied intermittent current pulses. They thus provide a new means for the facilitation of the effects of epidural stimulation.

Presynaptic actions of transcranial and local direct current stimulation in the red nucleus.

The main aim of the present study was to examine to what extent long-lasting subcortical actions of transcranial direct current stimulation (tDCS) may be related to its presynaptic actions. This was investigated in the red nucleus, where tDCS was recently demonstrated to facilitate transmission between interpositorubral and rubrospinal neurons. Changes in the excitability of preterminal axonal branches of interpositorubral neurons close to rubrospinal neurons were investigated during and after tDCS (0.2 mA) applied over the sensorimotor cortical area in deeply anaesthetized rats and cats. As a measure of the excitability, we used the probability of antidromic activation of individual interpositorubral neurons by electrical stimuli applied in the red nucleus. Our second aim was to compare effects of weak (≤1 µA) direct current applied within the red nucleus with effects of tDCS to allow the use of local depolarization in a further analysis of mechanisms of tDCS instead of widespread and more difficult to control depolarization evoked by distant electrodes. Local cathodal polarization was found to replicate all effects of cathodal tDCS hitherto demonstrated in the rat, including long-lasting facilitation of trans-synaptically evoked descending volleys and trisynaptically evoked EMG responses in neck muscles. It also replicated all effects of anodal tDCS in the cat. In both species, it increased the excitability of preterminal axonal branches of interpositorubral neurons up to 1 h post-tDCS. Local anodal polarization evoked opposite effects. We thus show that presynaptic actions of polarizing direct current may contribute to both immediate and prolonged effects of tDCS.

Subcortical effects of transcranial direct current stimulation in the rat.

Transcranial direct current stimulation (tDCS) affects neurons at both cortical and subcortical levels. The subcortical effects involve several descending motor systems but appeared to be relatively weak, as only small increases in the amplitude of subcortically initiated descending volleys and a minute shortening of latencies of these volleys were found. The aim of the present study was therefore to evaluate the consequences of facilitation of these volleys on the ensuing muscle activation. The experiments were carried out on deeply anaesthetized rats without neuromuscular blockade. Effects of tDCS were tested on EMG potentials recorded from neck muscles evoked by weak (20-60 µA) single, double or triple stimuli applied in the medial longitudinal fascicle (MLF) or in the red nucleus (RN). Short latencies of these potentials were compatible with monosynaptic or disynaptic actions of reticulospinal and disynaptic or trisynaptic actions of rubrospinal neurons on neck motoneurons. Despite only weak effects on indirect descending volleys, the EMG responses from both the MLF and the RN were potently facilitated by cathodal tDCS and depressed by anodal tDCS. Both the facilitation and the depression developed relatively rapidly (within the first minute) but both outlasted tDCS and were present for up to 1 h after tDCS. The study thus demonstrates long-lasting effects of tDCS on subcortical neurons in the rat, albeit evoked by an opposite polarity of tDCS to that found to be effective on subcortical neurons in the cat investigated in the preceding study, or for cortical neurons in the humans.

The influence of a 5-wk whole body vibration on electrophysiological properties of rat hindlimb spinal motoneurons.

The study aimed at determining the influence of a whole body vibration (WBV) on electrophysiological properties of spinal motoneurons. The WBV training was performed on adult male Wistar rats, 5 days a week, for 5 wk, and each daily session consisted of four 30-s runs of vibration at 50 Hz. Motoneuron properties were investigated intracellularly during experiments on deeply anesthetized animals. The experimental group subjected to the WBV consisted of seven rats, and the control group of nine rats. The WBV treatment induced no significant changes in the passive membrane properties of motoneurons. However, the WBV-evoked adaptations in excitability and firing properties were observed, and they were limited to fast-type motoneurons. A significant decrease in rheobase current and a decrease in the minimum and the maximum currents required to evoke steady-state firing in motoneurons were revealed. These changes resulted in a leftward shift of the frequency-current relationship, combined with an increase in slope of this curve. The functional relevance of the described adaptive changes is the ability of fast motoneurons of rats subjected to the WBV to produce series of action potentials at higher frequencies in a response to the same intensity of activation. Previous studies proved that WBV induces changes in the contractile parameters predominantly of fast motor units (MUs). The data obtained in our experiment shed a new light to possible explanation of these results, suggesting that neuronal factors also play a substantial role in MU adaptation.

A prospective randomized trial: a comparison of the analgesic effect and toxicity of 153Sm radioisotope treatment in monotherapy and combined therapy including local external beam radiotherapy (EBRT) among metastatic castrate resistance prostate cancer (mCRPC) patients with painful bone metastases.

Bone metastases in prostate cancer constitute the most frequent cause of systemic failure in treatment, which results in numerous complications and finally leads to patient's death. Pain is one of the first and most important clinical symptoms of bone metastases and can be found among more than 80% of patients. Therefore, the most analgetic effective and simultaneously the least toxic treatment is an important point of therapeutic management in this group of patients. The aim of this prospective clinical trial was a comparison of analgetic effectiveness and toxicity of monotherapy with 153Sm isotope to combined therapy (153Sm + EBRT) among patients diagnosed with multiple painful bone metastases due to CRPC (mCRPC). 177 patients with mCRPC were included into the prospective randomised clinical trial in which 89 patients were assigned to the 153Sm isotope monotherapy, while 88 patients were assigned to the combined therapy including 153Sm isotope therapy and EBRT. All patients were diagnosed (bone scan and X-ray or/and CT or/and MRI) with painful bone metastases (bone pain intensity >= 6 according to VAS classification). The following additional inclusion criteria were established: histologically confirmed adenocarcinoma of prostate, multifocal bone metastases, no prior chemotherapy or palliative radiotherapy to bone. All patients signed informed consent.The combination of the isotope therapy with EBRT was more effective analgetic treatment than isotope therapy alone. The highest pain decline was noticed in the first weeks after treatment termination. In the whole group, a total or partial analgesic effect was observed among 154 (87%) patients while among 23 (13%) patients there was a lack of analgesic effect or even pain intensification. The results of this clinical trial demonstrated that for patients with multiple mCRPC it is recommended to combine the 153Sm isotope therapy with local EBRT because of a greater analgetic effect. It is important to note that combined therapy did not intensify the toxicity of treatment.

Iodine prophylaxis intensification. Influence on radioiodine uptake and activity of 131I used in the treatment of hyperthyroid patients with Graves' disease.

UNLABELLED: Poland, a country with mild/moderate iodine deficiency introduced an obligatory iodination salt system in 1996. AIM: To compare the results of radioiodine (131I) uptake after 5 h and 24 h with the activity of radioiodine used in the treatment of hyperthyroid patients with Graves' disease in the years 1995 and 2003. PATIENTS, METHODS: The marker of iodine content in the diet was urinary iodine excretion. 1000 randomly chosen patients (average age: 46 +/- 12 years) were included in the study. Every patient had routinely estimated radioiodine uptake after 5 h and 24 h and the activity of 131I was calculated using scintigraphy and ultrasonography of the thyroid gland. Urinary iodine excretion in samples from year 1995 and 2003 was also determined in some patients and healthy volunteers. RESULTS: The iodine load in the diet increased from 66 microg (average) in the year 1995 to 115 microg in the year 2003. Thyroid radioiodine uptake was 40% lower in comparison with the results from 1995. The average activity of 131I given in the year 2003 (10 mCi) was about 40% higher than in the year 1995 (7 mCi). CONCLUSION: There was significant negative correlation between higher iodine content in the diet and lower values of radioiodine uptake, which led to the application of the higher activity of 131I during treatment.

[The evaluation of goiter frequency and iodine prophylaxis efficiency in children population in Wielkopolska area from 1992 to 1998]. / Ocena czestosci wystepowania wola i skutecznosci profilaktyki jodowej u dzieci na terenie Wielkopolski w latach 1992-1998.

The aim of the study was to compare the current state and efficiency of iodine prophylaxis during the last six years. The study included 800 children from the rural and urban area (462 children in 1992 and 338 children in 1998) with the proportional sex and age (8-13 years) distribution, 24.936 newborns (9875 in 1992/1993 and 15.061 - mostly in the early part of 1998). The thyroid size (by USG), serum thyroglobulin (TG) concentration, urinary iodine (UI) concentration, %age of neonatal-TSH above 5 micro U/ml were evaluated using current ICCIDD and WHO criteria. The prevalence of goiter detected in children population in 1992 was 26% (recount by current criteria), in the early part of 1998 it was reduced to 21%. Parallelly, mean urinary iodine concentration increased from 49 micro g/l to 79 micro g/l. The reduction of goiter prevalence was associated with the reduction of mean serum thyroglobulin concentration from 26 ng/ml to 18 ng/ml. In the group of newborns the %age of TSH results above 5 micro U/ml decreased from 6 to 2.6%. Generally, the study proved significant increase of iodine prophylaxis efficiency in Wielkopolska Region in the period of the last six years, but it is still the area with mild iodine deficiency, which suggests the necessity of using other forms of iodine prophylaxis except for salt iodization. The obtained results suggest the necessity to extend the study on the role of other goitrogenic factors, which are probably present in the whole Wielkopolska Region.

[The efficiency of goiter prevention due to iodine deficiency in pregnant women]. / Skutecznosc profilaktyki wola z niedoboru jodu u kobiet ciezarnych.

The iodine is indispensable element for life that is also fundamental substract for thyroid hormone synthesis which make very important influence on protein's lipid's, carbohydrate's and highly caloric substances metabolism and are a requisite of proper man development. The pregnant women are one of population group which is the most sensitive on iodine's deficiency. The results of researches indicate on insufficient iodine intake in pregnant women diet, whose take food even according to diet's recommendation given by physician. The wide iodine's prophylaxis which was provided as yet is insufficient in case of pregnant and nursing women. It is confirmed the necessity of additional iodine supplementation. A set of control tests should be done in requires cases that inform physician about changes in function and size of thyroid gland and make possible the individualization of treatment. The supplementation doses of iodine about 150 micrograms are safe and there was not observed any side effects during their taking.

The results of epidemiological studies concerning iodine deficiency and goiter in Poznan Region (Poznan coordinating center).

The studies concerning iodine deficiency and occurrence of goiter, being a fragment of the program covering different parts of Poland, included 2620 children of age between 7 and 12 years attending randomly chosen schools situated in towns and villages of Poznan, Pila, Leszno, Konin, Kalisz, Bydgoszcz and Zielona Góra districts. Among the children studied, 1009 children (522 boys and 487 girls) attended town schools, and 1611 (774 boys and 837 girls) country schools. All children were subjected to anamnesis by using a standard questionnaire. Also physical examination of the thyroid aimed at the evaluation of size and morphology of the gland was carried out by palpation (according to the obligatory WHO scale) and by ultrasonography. Urine samples were taken from the majority of children for the determination of urinary excretion of iodine. In 736 (28.1%) of the studied children an enlargement of the thyroid was found. Among these children 253 are inhabitants of towns (this number represents 27.8% of all urban children studied) and 483 are inhabitants of villages (30% of all rural children studied). In 92.7% of cases the goiter could be classified as type IB according to WHO and in 56 cases it was of nodular character. There was a clear relation between the incidence of goiter and the age of the children studied. Frequency distribution of goiter in the individual age groups was as follows: for urban children--21.8% in age group of 7-8 years, 23.5% in age group of 9-10 years and 29.7% in age group 11-12 years, and for rural children the corresponding values were 21.1%, 30.2% and 38.2%. Mean urinary iodine excretion was 96 micrograms/L (median 84 micrograms/L) for urban children, and 87 micrograms/L (median 64 micrograms/L) for rural children. Among 2620 answers concerning the use of iodized salt in the household, only 980 (37.1%) were positive. In towns, the use of iodized salt declared about 41% of families and in villages about 35%. Altogether, among 736 cases of goiter, 464 are children not using iodized salt. Only in 272 cases goiter appeared despite the use of iodized salt. The data concerning family occurrence of goiter and the type of iodized salt used can be treated as approximate because of subjective character. According to the results obtained, the region covered by the study falls according to the WHO and ICCIDD classification to the category of an area of mild iodine deficiency requiring more intensive iodine prophylaxis.