Unmet Needs and Pro-health Behavior in Patients with Chronic Respiratory Diseases.

Coordinated healthcare paradigm addressing the biopsychosocial spheres of patients seems advantageous for the management of chronic diseases. The purpose of the study was to determine the influence of unmet needs on pro-health behavior in chronic respiratory diseases and to recognize the factors that help identify the unmet needs. The patients were asked to complete the Camberwell Assessment of Needs Inventory and the Health Behavior Inventory. The study group consisted of 171 adult patients with chronic respiratory diseases. The study participants were recruited from among the patients of 130 general practitioners between July 2011 and March 2016. The findings of this study indicate that any prevention program should focus on increasing the level of satisfied needs in patients with chronic respiratory diseases. For the most effective treatment, fragmented and disease-focused processes should be replaced by integrated health and social care. We conclude that the treatment process that involves interdisciplinary clinical approach, which, aside from the physical treatment, could recognize and address the psychological aspects of unmet needs would be conducive to undertake pro-health behavior by pulmonary patients.

Patient-specific 3D models aid planning for triplane proximal femoral osteotomy in slipped capital femoral epiphysis.

PURPOSE: Slipped capital femoral epiphysis (SCFE) can result in a complex three-dimensional (3D) deformity of the proximal femur. A three-plane proximal femoral osteotomy (TPFO) has been described to improve hip mechanics. The purpose of this study was to evaluate the benefits of using 3D print technology to aid in surgical planning. PATIENTS AND METHODS: Fifteen children treated with TPFO for symptomatic proximal femoral deformity due to SCFE were included in this study. Ten patients were treated by a single surgeon with (model group, n = 5) or without (no-model group, n = 5) a 3D model for pre-operative planning, and compared with patients treated by two senior partners without the use of a model (senior group, n = 5) to evaluate for a learning curve. Peri-operative data including patient body mass index (BMI), surgical time and fluoroscopy time were recorded. RESULTS: Children in all three groups had similar BMIs at the time of the TPFO. Post-operative radiographic parameters were equally improved in all three groups. On average, surgical time decreased by 45 minutes and 38 minutes, and fluoroscopy time decreased by 50% and 25%, in the model group compared with the no-model and senior groups, respectively. CONCLUSIONS: Patient-specific 3D models aid in surgical planning for complex 3D orthopaedic deformities by enabling practice of osteotomies. Results suggest that 3D models may decrease surgical time and fluoroscopy time while allowing for similar deformity correction. These models may be especially useful to overcome steep learning curves for complex procedures or in trainee education through mock surgical procedures.

The influence of the time-of-day administration of sunitinib on the penetration through the blood-brain and blood-aqueous humour barriers in rabbits.

OBJECTIVE: Sunitinib is a multiple tyrosine kinase inhibitor (TKI) that exerts anti-tumor and antiangiogenic activity. It is used for the treatment of metastatic gastrointestinal stromal tumours, renal cell carcinoma and pancreatic neuroendocrine tumours. A few studies confirm the anti-tumour activity of sunitinib in brain tumours and uveal melanoma, as well as its efficacy in the reduction of brain metastases of some primary cancers. Therefore, the penetration of sunitinib through the blood-brain barrier (BBB) and blood-aqueous humour barrier (BAB) is an issue of growing interest. The aim of the study was to investigate the influence of the time-of-day administration on the penetration of sunitinib into the cerebrospinal fluid (CSF) and aqueous humour (AH). MATERIALS AND METHODS: The rabbits were divided into two groups: I (control group)--receiving sunitinib at 8 a.m., and II--receiving sunitinib at 8 p.m. Sunitinib was administered p.o. at a single dose of 25 mg. The concentrations of sunitinib and its active metabolite (SU12662) in the plasma, CSF, AH were measured with the validated HPLC-UV method. RESULTS: The plasma AUC0-t for sunitinib in group I was 2051.8 ng × h/mL, whereas in group II it was 3069.3 ng × h/mL. The aqueous humour AUC0-t for sunitinib in thr groups were 43.2 and 76.3 ng × h/mL, respectively. The cerebrospinal AUC0-t for sunitinib in groups I and II were 55.5 and 66.3 ng × h/mL, respectively. CONCLUSIONS: After the evening administration (8 p.m.) the exposure to sunitinib in the rabbits' plasma, AH and CSF was higher than after the morning administration (8 a.m.), but the degree of sunitinib penetration through the BAB and BBB was very low (< 5%) and comparable in both groups.

Isolation of three dibenzocyclooctadiene lignans from in vitro cultures of Schisandra chinensis (Turcz.) Baill.--the first report.

Three dibenzocyclooctadiene lignans: deoxyschizandrin (1), gomisin A (2) and schizandrin (3) were isolated from biomass extracts of Schisandra chinensis (Turcz.) Baill. shoot-differentiating callus cultures. The mentioned lignans were not isolated earlier from in vitro cultures of this plant species. This is the first report concerning on isolation of dibenzocyclooctadiene lignans from in vitro cultures of Schisandra chinensis.

Health-related quality of life, optimism, and coping strategies in persons suffering from localized scleroderma.

The clinical course of localized scleroderma may consist of bodily deformations, and bodily functions may also be affected. Additionally, the secondary lesions, such as discoloration, contractures, and atrophy, are unlikely to regress. The aforementioned symptoms and functional disturbances may decrease one's quality of life (QoL). Although much has been mentioned in the medical literature regarding QoL in persons suffering from dermatologic diseases, no data specifically describing patients with localized scleroderma exist. The aim of the study was to explore QoL in localized scleroderma patients and to examine their coping strategies in regard to optimism and QoL. The study included 41 patients with localized scleroderma. QoL was evaluated using the SKINDEX questionnaire, and levels of dispositional optimism were assessed using the Life Orientation Test-Revised. In addition, individual coping strategy was determined using the Mini-MAC scale and physical condition was assessed using the Localized Scleroderma Severity Index. The mean QoL score amounted to 51.10 points, with mean scores for individual components as follows: symptoms = 13.49 points, emotions = 21.29 points, and functioning = 16.32 points. A relationship was detected between QoL and the level of dispositional optimism as well as with coping strategies known as anxious preoccupation and helplessness-hopelessness. Higher levels of optimism predicted a higher general QoL. In turn, greater intensity of anxious preoccupied and helpless-hopeless behaviors predicted a lower QoL. Based on these results, it may be stated that localized scleroderma patients have a relatively high QoL, which is accompanied by optimism as well as a lower frequency of behaviors typical of emotion-focused coping strategies.

Short- and medium-chain fatty acids as a feed supplement for weaning and nursery pigs.

The effect of supplementing piglet diets with acidifiers containing the short-chain fatty acids - SCFA (propionic C3 and formic) together with medium-chain fatty acids -- MCFA (caprylic C8 and capric C10) on performance, nutrient apparent digestibility, intestinal microflora and small intestine structure was investigated. The study was performed on 326 piglets allocated to 5 experimental groups. They were fed a standard diet (Group I - control) or a standard diet supplemented with 0.5% propionic and formic acids (Group II - PF). Group III (PF + C8), group IV (PF + C10) and group V (PF + C8 + C10) received the same mixture as group II with a supplement of 0.2% of caprylic and/or capric acids, respectively. Apparent digestibility of nutrients and microbiological analyses were performed. The structure of jejunum mucosa was also examined. Piglets receiving capric acid (groups IV and V) had the highest body weight gains. Piglets receiving MCFA digested protein and fiber better (P < or = 0.05) than piglets receiving SCFA as acidifier. There was no difference in intestinal microflora except for Clostridium perfringens, the population of which was reduced by SCFA (group II). Villi of the mucosal epithelium were the highest (P < or = 0.05) in piglets receiving SCFA with capric acid (group IV). Under the conditions of this study a mixture of SCFA (propionic and formic) with capric acid significantly improves performance of piglets.

Enhancement of local superconductivity in ferromagnetic FeCrB metallic glass by Ar+ ion irradiation.

We have reinforced local superconductivity in ferromagnetic Fe(67)Cr(18)B(15) metallic glasses by ion irradiation. Superconductivity in this medium appears due to the presence of large-scale layered clusters of metallic Fe-Cr phase, 150-230 Å in size, with a ferromagnetic (or superparamagnetic) Fe-rich core and nonmagnetic Cr-rich superconducting shell. Here we show that due to the intensification of concentration phase separation in the Fe-Cr clusters under ion (Ar(+)) irradiation, the volume of the superconducting phase increases from the initial 0.4-0.5% up to 7-8%. After irradiation, the resistivity jump Δρ/ρ in the temperature range T=3.1-3.6 K increases ∼14 times, reaching 19%, as compared to 1.36% for the initial sample. In the interval of T=3.1-3.6 K, the rate of resistance change reaches 79% K(-1) for the irradiated sample instead of 3.6% K(-1) for the initial sample. In the same temperature interval, the rate of magnetoresistance change increases from 3% K(-1) for the initial sample up to 70% K(-1) after irradiation.

Low-temperature anomalies in resistance and magnetoresistance of amorphous FeCrB ribbons. Coexistence of ferromagnetism and local superconductivity?

Investigation of the conductivity mechanisms in ferromagnetic Fe(67)Cr(18)B(15) metallic glasses with clusterized structure reveals anomalies in the behaviour of resistance and magnetoresistance (MR) in a narrow temperature interval, T = 3.6-3.1 K. The anomalies are seen as a sharp decrease of the sample resistivity in this range, with a rate equal to 3.6% K(-1), i.e. 200-500 times more than the rate 0.008-0.021% K(-1) in the range of 300-4 K. MR in the same range increases with a rate 1000 times larger (4% K(-1) at T ∼ 3.1-3.6 K) than in the 300-4 K range (<0.0015% K(-1)). We explain this result by the appearance of local superconductivity in the large-scale layered clusters of metallic Fe-Cr phase, 150-200 Å in size, with ferromagnetic Fe(2)Cr core and nonmagnetic FeCr(2) superconducting shell. The superconducting phase, which occupies 0.4-0.5% of the sample volume, provides a resistance jump Δρ/ρ≈1.5% that corresponds to calculation. The superconducting state of the clusters collapses if the magnetic field exceeds 20 kOe.

Free phenolic acids in Ruta graveolens L. in vitro culture.

Eight phenolic acids were determined using HPLC method in methanolic extracts of Ruta graveolens L. (Rutaceae) shoots cultured in vitro on four variants of Linsmaier and Skoog (LS) medium differing in contents of growth regulators, NAA and BAP (ranging between 0.1-3.0 mg/l). Four compounds: protocatechuic, vanillic, syringic and p-coumaric acid were detected and quantified. The total content of metabolites was dependent on LS medium variants. The contents of protocatechuic acid, quantitatively dominating on all tested LS medium variants, were considerable (from 67.15 to 93.24 mg/100 g d.w.) in comparison with its contents in the plant material under analysis (46.36 to 218.27 mg/ 100 g d.w.). This is the first report of the isolation of protocatechuic acid from an in vitro plant culture.

Large-conductance K+ channel openers induce death of human glioma cells.

Large-conductance Ca(2+)-activated K(+) channels (BKCa channels) are highly expressed in human glioma cells. It has been reported that BK(Ca) channels are present in the inner mitochondrial membrane of the human glioma cell line LN229. In the present study we investigated whether BK(Ca)-channel openers, such as CGS7181 (ethyl 2-hydroxy-1-[[(4-methylphenyl)amino]oxo]-6-trifluoromethyl-1H-indole-3-carboxylate) and CGS7184 (ethyl 1-[[(4-chlorophenyl)amino]oxo]-2-hydroxy-6-trifluoromethyl-1H-indole-3-carboxylate), affect the functioning of LN229 glioma cell mitochondria in situ. In the micromolar concentration range CGS7181 and CGS7184 induced glioma cell death. Morphological and cytometric analyses confirmed that both substances trigger the glioma cell death. This effect was not inhibited by the pan-caspase inhibitor z-VAD-fmk. Lack of DNA laddering, PARP cleavage, and caspase 3 activation suggested that glioma cell death was not of the apoptotic type. We examined the effect of CGS7184 on mitochondrial membrane potential and mitochondrial respiration. Potassium channel opener CGS7184 increased cell respiration and induced mitochondrial membrane depolarization. The latter was dependent on the presence of Ca(2+) in the external medium. It was shown that CGS7184 induced an increase of cytosolic Ca(2+) concentration due to endoplasmic reticulum store depletion. In conclusion, our results show that CGS7181 and CGS7184 induce glioma cell death by increasing the cytosolic calcium concentration followed by activation of calpains.

Differential distribution of Ca2+-activated potassium channel beta4 subunit in rat brain: immunolocalization in neuronal mitochondria.

Large conductance Ca(2+)-activated potassium channels (BK(Ca) channels) are expressed in the plasma membrane of various cell types. Interestingly, recent studies provided evidence for the existence of BK(Ca) channels also in mitochondria. However, the molecular composition of these channels as well as their cellular and tissue distribution is still unknown. The goal of the present study was to find a candidate for the regulatory component of the mitochondrial large conductance calcium activated potassium (mitoBK(Ca)) channel in neurons. A combined approach of Western blot analysis, high-resolution immunofluorescence and immunoelectron microscopy with the use of antibodies directed against four distinct beta subunits demonstrated the presence of the BK(Ca) channel beta4 subunit (KCNMB4) in the inner membrane of neuronal mitochondria in the rat brain and cultured neurons. Within the cell, the expression of beta4 subunit was restricted to a subpopulation of mitochondria. The analysis of beta4 subunit distribution throughout the brain revealed that the highest expression levels occur in the thalamus and the brainstem. Our results suggest that beta4 subunit is a regulatory component of mitochondrial BK(Ca) channels in neurons. These findings may support the perspectives for the neuroprotective role of mitochondrial BK(Ca) channel in specific brain structures.

Multiple magnetic phase transitions in Tb(3)Cu(4)Si(4).

A polycrystalline sample of Tb(3)Cu(4)Si(4) was investigated by means of magnetometric, electrical resistivity, thermopower and heat capacity measurements. This paper also includes reanalyses of former neutron diffraction data. The compound crystallizes in a Gd(3)Cu(4)Ge(4)-type orthorhombic structure (Immm space group), in which the Tb ions occupy two inequivalent sites (2d and 4e). The bulk results indicate that these two magnetic sublattices order antiferromagnetically at different temperatures, in agreement with the neutron diffraction data.

Quinine inhibits mitochondrial ATP-regulated potassium channel from bovine heart.

The mitochondrial ATP-regulated potassium (mitoK(ATP) channel has been suggested as trigger and effector in myocardial ischemic preconditioning. However, molecular and pharmacological properties of the mitoK(ATP) channel remain unclear. In the present study, single-channel activity was measured after reconstitution of the inner mitochondrial membrane from bovine ventricular myocardium into bilayer lipid membrane. After incorporation, a potassium-selective current was recorded with mean conductance of 103 +/- 9 pS in symmetrical 150 mM KCl. Single-channel activity of this reconstituted protein showed properties of the mitoK(ATP) channel: it was blocked by 500 microM ATP/Mg, activated by the potassium-channel opener diazoxide at 30 microM, inhibited by 50 microM glibenclamide or 150 microM 5-hydroxydecanoic acid, and was not affected by the plasma membrane ATP-regulated potassium-channel blocker HMR1098 at 100 microM. We observed that the mitoK(ATP) channel was blocked by quinine in the micromolar concentration range. The inhibition by quinine was additionally verified with the use of 86Rb+ flux experiments and submitochondrial particles. Quinine inhibited binding of the sulfonylurea derivative [3H]glibenclamide to the inner mitochondrial membrane. We conclude that quinine inhibits the cardiac mitoK(ATP) channel by acting on the mitochondrial sulfonylurea receptor.

Protective effects of the potassium channel opener-diazoxide against injury in neonatal rat ventricular myocytes.

The mitochondrial ATP-regulated potassium channel is present in the inner membrane of heart mitochondria. Similarly to plasma membrane K(ATP), the mitochondrial channel is inhibited by antidiabetic sulfonylureas and activated by potassium channel openers, such as diazoxide. In the present work, the cytoprotective properties of diazoxide on the H9c2 cardiac myoblast cell line and neonatal rat ventricular cardiomyocytes were analysed. It was observed that 100 micromol/l diazoxide protected neonatal rat ventricular cardiomyocytes, but not H9c2 myoblasts, against injury induced by hydrogen peroxide or simulated ischemia. Moreover, diazoxide prevented hydrogen peroxide-induced mitochondrial potential depolarisation in neonatal rat ventricular cardiomyocytes. Diazoxide, at the same time, did not affect the expression level of the anti-apoptotic protein bcl-2 in these cells. The protective effects of diazoxide were suppressed by 5-hydroxydecanoic acid, a potassium channel blocker. These observations suggest that activation of the mitochondrial ATP-regulated potassium channel plays an important role in protection of neonatal cardiomyocytes against injury.

Intracellular potassium and chloride channels: an update.

Channels selective for potassium or chloride ions are present in all intracellular membranes such as mitochondrial membranes, sarcoplasmic/endoplasmic reticulum, nuclear membrane and chromaffin granule membranes. They probably play an important role in events such as acidification of intracellular compartments and regulation of organelle volume. Additionally, intracellular ion channels are targets for pharmacologically active compounds, e.g. mitochondrial potassium channels interact with potassium channel openers such as diazoxide. This review describes current observations concerning the properties and functional roles of intracellular potassium and chloride channels.

ATP-sensitive K+ transport in adrenal chromaffin granules.

In the present study the influx of 86Rb+, a K+ analogue, was studied in mitochondria, microsomes and chromaffin granules prepared from adrenal gland medulla. The most active electrogenic 86Rb+ transport was found in the membrane fraction identified as chromaffin granules by marker enzyme estimation. The transport was found to be sensitive to ATP, ATP gamma S, ADP and to the triazine dyes, but not to AMP and cAMP. The inhibition induced by ATP was observed in the absence of externally added Mg2+, suggesting that a free nucleotide, rather than the ATP-Mg complex, was required for inhibition. Furthermore, the 86Rb+ influx was found to be inhibited by Mg2+ alone, but not by Ca2+ and antidiabetic sulfonylureas. The 86Rb+ influx was not stimulated by potassium channel openers. In conclusion, our results indicate that an electrogenic, ATP-sensitive potassium transport system operates in the chromaffin granule membrane.

Potassium channel openers depolarize hippocampal mitochondria.

We investigated the effect of the potassium channel openers diazoxide and RP66471 on mitochondrial membrane potential and mitochondrial respiration in digitonin-treated rat hippocampal homogenates. Both diazoxide and RP66471 induced a dose-dependent decrease of mitochondrial membrane potential. Concomitant with the depolarization was an increase of mitochondrial respiration. Furthermore, the mitochondrial membrane depolarization induced by diazoxide and RP66471 was significantly larger in the presence of potassium ions than in the presence of sodium ions. The diazoxide-induced (but not RP66471-induced) mitochondrial membrane depolarization was partially inhibited by blockers of the ATP-regulated potassium channel, 5-hydroxydecanoic acid or the antidiabetic sulfonylurea glibenclamide. In addition, the potassium channel openers diazoxide and RP66471 increased mitochondrial matrix volume and induced a release of cytochrome c from hippocampal mitochondria. These results indicate the presence of a mitochondrial ATP-regulated potassium channel in rat hippocampus being a target for potassium channel openers.