Risk factors for glucose intolerance in active acromegaly

In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33%) had diabetes mellitus and 2 (5%; 1-16%) impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test). A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection) was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

Limited-sampling strategy models for estimating the pharmacokinetic parameters of 4-methylaminoantipyrine, an active metabolite of dipyrone

Bioanalytical data from a bioequivalence study were used to develop limited-sampling strategy (LSS) models for estimating the area under the plasma concentration versus time curve (AUC) and the peak plasma concentration (Cmax) of 4-methylaminoantipyrine (MAA), an active metabolite of dipyrone. Twelve healthy adult male volunteers received single 600 mg oral doses of dipyrone in two formulations at a 7-day interval in a randomized, crossover protocol. Plasma concentrations of MAA (N = 336), measured by HPLC, were used to develop LSS models. Linear regression analysis and a "jack-knife" validation procedure revealed that the AUC0-¥ and the Cmax of MAA can be accurately predicted (R²>0.95, bias <1.5%, precision between 3.1 and 8.3%) by LSS models based on two sampling times. Validation tests indicate that the most informative 2-point LSS models developed for one formulation provide good estimates (R²>0.85) of the AUC0-¥ or Cmax for the other formulation. LSS models based on three sampling points (1.5, 4 and 24 h), but using different coefficients for AUC0-¥ and Cmax, predicted the individual values of both parameters for the enrolled volunteers (R²>0.88, bias = -0.65 and -0.37%, precision = 4.3 and 7.4%) as well as for plasma concentration data sets generated by simulation (R²>0.88, bias = -1.9 and 8.5%, precision = 5.2 and 8.7%). Bioequivalence assessment of the dipyrone formulations based on the 90% confidence interval of log-transformed AUC0-¥ and Cmax provided similar results when either the best-estimated or the LSS-derived metrics were used.

Evaluation of behavioral states among morning and evening active healthy individuals

The Horne-Östberg questionnaire partly covers some factors that may be important determinants of peak time and characterize patterns of behavior. We conducted a study for the evaluation of self-reported behavioral states (hunger sensation, availability for study, physical exercise, solving daily problems, and time preferences) as expressions of underlying cyclic activity. Three hundred and eighteen community subjects without history of medical, psychiatric, or sleep disorders were evaluated in a cross-sectional design. A self-report about daily highest level of activity was used to categorize individuals into morning, evening, and indifferently active. Time-related behavioral states were evaluated with 23 visual analog questions. The responses to most analogic questions were significantly different between morning and evening active subjects. Logistic regression analysis identified a group of behaviors more strongly associated with the self-reported activity pattern (common wake up time, highest subjective fatigue, as well as wake up, bedtime, exercise and study preferences). These findings suggested that the patterns of activity presented by normal adults were related to specific common behavioral characteristics that may contribute to peak time.

Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ß-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL) when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL) than in controls (237.1 ± 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

Modular Double-Cascade Converter

Medium-voltage motor drives extend the power rating of AC motor drives in industrial applications. Multilevel converters are gaining an ever-stronger foothold in this field. This doctoral dissertation introduces a new topology to the family of modular multilevel converters: the modular double-cascade converter. The modularity of the converter is enabled by the application of multiwinding mediumfrequency isolation transformers. Owing to the innovative transformer link, the converter presents many advantageous properties at a concept level: modularity, high input and output power quality, small footprint, and wide variety of applications, among others. Further, the research demonstrates that the transformer link also plays a key role in the disadvantages of the topology. An extensive simulation study on the new converter is performed. The focus of the simulation study is on the development of control algorithms and the feasibility of the topology. In particular, the circuit and control concepts used in the grid interface, the coupling configurations of the load inverter, and the transformer link operation are thoroughly investigated. Experimental results provide proof-of-concept results on the operation principle of the converter. This work concludes a research collaboration project on multilevel converters between LUT and Vacon Plc. The project was active from 2009 until 2014.

Effectiveness of highly active antiretroviral therapy using non-brand name drugs in Brazil

In Brazil, HIV-infected individuals receive drugs (including non-brand name drugs which comprise locally produced generics and drugs that have not been tested in bioequivalence trials) free of charge from the government. The objective of the present study was to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in Rio de Janeiro, Brazil, where non-brand drugs are widely used. For this purpose, we estimated the proportion of subjects with virologic failure (plasma HIV viral load greater than 400 copies/mL at 6 months after initiation of treatment). This was a retrospective cohort study of drug-naive HIV-infected subjects who initiated HAART. Subjects were included in the analysis if they were 18 years of age or older, were treatment naive, started HAART with a minimum of 3 drugs, and had available information on blood plasma HIV-1 viral load after 6 months on therapy. All subjects used antiretrovirals in dosing regimens recommended by the Brazilian National Advisory Committee for Antiretroviral Therapy. Chart reviews were conducted in three settings: at two public health outpatient units, at one clinical trial unit and at one private office. No comparisons of the effectiveness of non-brand name with the effectiveness of brand name drugs were made. We present results for 485 patients; of these, 354 (73%), 55 (11%), and 76 (16%) were seen at the public health outpatient units, private office, and clinical trial unit, respectively. Virologic failure was observed in 119 (25%) of the subjects. This study demonstrates the effectiveness of HAART in a setting where non-brand name drugs are widely used.

Expression and purification of the immunogenically active fragment B of the Park Williams 8 Corynebacterium diphtheriae strain toxin

The construction of a hexahistidine-tagged version of the B fragment of diphtheria toxin (DTB) represents an important step in the study of the biological properties of DTB because it will permit the production of pure recombinant DTB (rDTB) in less time and with higher yields than currently available. In the present study, the genomic DNA of the Corynebacterium diphtheriae Park Williams 8 (PW8) vaccine strain was used as a template for PCR amplification of the dtb gene. After amplification, the dtb gene was cloned and expressed in competent Escherichia coli M15™ cells using the expression vector pQE-30™. The lysate obtained from transformed E. coli cells containing the rDTB PW8 was clarified by centrifugation and purified by affinity chromatography. The homogeneity of the purified rDTB PW8 was confirmed by immunoblotting using mouse polyclonal anti-diphtheria toxoid antibodies and the immune response induced in animals with rDTB PW8 was evaluated by ELISA and dermonecrotic neutralization assays. The main result of the present study was an alternative and accessible method for the expression and purification of immunogenically reactive rDTB PW8 using commercially available systems. Data also provided preliminary evidence that rabbits immunized with rDTB PW8 are able to mount a neutralizing response against the challenge with toxigenic C. diphtheriae.

Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active α1B-adrenoceptors

The regulatory function of α1B-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na+/K+-ATPase and Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant α1B-adrenoceptor (CAMα1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30% in CAMα1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na+/K+-ATPase activity nor the expression of α1 and α2 subunit isoforms was changed in CAMα1B-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac α1B-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.

Protein turnover, amino acid requirements and recommendations for athletes and active populations

Skeletal muscle is the major deposit of protein molecules. As for any cell or tissue, total muscle protein reflects a dynamic turnover between net protein synthesis and degradation. Noninvasive and invasive techniques have been applied to determine amino acid catabolism and muscle protein building at rest, during exercise and during the recovery period after a single experiment or training sessions. Stable isotopic tracers (13C-lysine, 15N-glycine, ²H5-phenylalanine) and arteriovenous differences have been used in studies of skeletal muscle and collagen tissues under resting and exercise conditions. There are different fractional synthesis rates in skeletal muscle and tendon tissues, but there is no major difference between collagen and myofibrillar protein synthesis. Strenuous exercise provokes increased proteolysis and decreased protein synthesis, the opposite occurring during the recovery period. Individuals who exercise respond differently when resistance and endurance types of contractions are compared. Endurance exercise induces a greater oxidative capacity (enzymes) compared to resistance exercise, which induces fiber hypertrophy (myofibrils). Nitrogen balance (difference between protein intake and protein degradation) for athletes is usually balanced when the intake of protein reaches 1.2 g·kg-1·day-1 compared to 0.8 g·kg-1·day-1 in resting individuals. Muscular activities promote a cascade of signals leading to the stimulation of eukaryotic initiation of myofibrillar protein synthesis. As suggested in several publications, a bolus of 15-20 g protein (from skimmed milk or whey proteins) and carbohydrate (± 30 g maltodextrine) drinks is needed immediately after stopping exercise to stimulate muscle protein and tendon collagen turnover within 1 h.

Chemical, biochemical, and microbiological aspects of chitosan quaternary salt as active coating on sliced apples

The biocompatibility of chitosan and chitosan quaternary salt coatings was evaluated for use as edible coatings for sliced apple. Measurement of water loss, color change, and fungal growth appearance were monitored as a function of time. A significant brownish effect was observed on chitosan coated slices, varying greatly from L* = 76.5 and Hue angle = 95.9° (t = 0) to L* = 45.3 and Hue angle = 69.8° (t = 3 days), whilst for TMC coated samples the variation was considerable lower (L* = 74.1; Hue angle = 95.0°) to (L* = 67.0; Hue angle = 83.8°) within the same period. The hydrosoluble derivative N,N,N-trimethylchitosan demonstrated good antifungal activity against P. expansum although highly dependent on the polymer properties such as degree of quaternization. The most efficient formulation was that prepared from derivative having a degree of quaternization of 45%, high solubility, and high viscosity. This formulation restrained fungus spreading up to 30%, while for the control it reached almost 80% of the total assessed surfaces during 7 days of storage.

Is All Fair in Law and War? The Ambiguous Principle of Proportionality of Collateral Damage and the CIA Drone Attacks in Pakistan

Tutkielma käsittelee Yhdysvaltain CIAn miehittämättömiä lennokki-iskuja Pakistanissa kansainvälisen humanitaarisen oikeuden suhteellisuusperiaatteen näkökulmasta. Suhteellisuusperiaatteen mukaan aseellisista iskuista saatavan sotilaallisen hyödyn tulee olla suhteellinen verrattuna siviileille aiheutuvaan haittaan. CIAn iskuja Pakistanissa on kritisoitu, että ne eivät täytä suhteellisuusperiaatteen asettamia vaatimuksia. Tutkielmassa perehdytään ensinnäkin selvittämään ne velvollisuudet, jotka suhteellisuusperiaate asettaa hyökkääjille. Sen jälkeen CIAn lennokki-iskuja tutkitaan näiden velvollisuuksien valossa. Tutkielmassa pyritään selvittämään antaako suhteellisuusperiaatteen luomat oikeudelliset velvollisuudet riittävää suojaa Pakistanin siviileille lennokki-iskujen tuhoja vastaan. Lisäksi pyritään selvittämään, onko lennokki-iskuissa viitteitä suhteellisuusperiaatteen vastaisista iskuista. Tutkimusmenetelmänä käytetään positivistista lainopin metodia, jonka avulla selvitetään voimassa olevaa kansainvälisen humanitaarisen tapaoikeuden suhteellisuusperiaatteen sisältöä. Oikeudellisina lähteinä käytetään pääasiassa humanitaarista tapaoikeutta, mutta tulkinnallisena apuna myös kansainvälisiä sopimuksia sekä oikeuden päätöksiä. Lisäksi oikeudellinen kirjallisuus on tutkimuksessa tärkeässä asemassa. Tutkimuksessa päädytään siihen, että suhteellisuusperiaatteen asettamat velvollisuudet hyökkääjälle ovat niin epämääräiset, että ne eivät anna riittävää suojaa siviileille. Ensinnäkin hyökkääjä voi määrittää sotilaallisen hyödyn omien päämääriensä mukaisesti suhteellisuusanalyysissä. Lisäksi kynnys sille, mikä katsotaan suhteellisuusperiaatteen vastaisuudeksi on hyvin epämääräinen ja korkea. Tämän vuoksi varotoimenpiteet iskujen suunnittelussa ovat hyvin tärkeässä asemassa myös suhteellisuusanalyysissä. Kuitenkin jos hyökkääjä edes jossain määrin osoittaa, että on tehnyt iskut hyvässä uskossa niiden laillisuudesta, iskujen katsotaan yleensä olevan suhteellisuusperiaatteen mukaisia. CIAn lennokki-iskuissa Pakistanissa on viitteitä suhteellisuusperiaatteen vastaisuudesta erityisesti ”tunnusmerkki-iskujen” osalta. ”Tunnusmerkki-iskut” johtavat yleensä vain vähäiseen sotilaalliseen hyötyyn aiheuttaen silti siviiliuhreja. Lisäksi erityisesti tunnusmerkki-iskuissa edellytetään korkeampaa tarkkuutta varotoimenpiteissä. Kuitenkin useat siviiliuhrit voivat merkitä sitä, että näitä varotoimenpiteitä ei ole noudatettu iskuissa.

Active Magnetic Bearing System Identification Methods and Rotor Model Updating

Active magnetic bearing is a type of bearing which uses magnetic field to levitate the rotor. These bearings require continuous control of the currents in electromagnets and data from position of the rotor and the measured current from electromagnets. Because of this different identification methods can be implemented with no additional hardware. In this thesis the focus was to implement and test identification methods for active magnetic bearing system and to update the rotor model. Magnetic center calibration is a method used to locate the magnetic center of the rotor. Rotor model identification is an identification method used to identify the rotor model. Rotor model update is a method used to update the rotor model based on identification data. These methods were implemented and tested with a real machine where rotor was levitated with active magnetic bearings and the functionality of the methods was ensured. Methods were developed with further extension in mind and also with the possibility to apply them for different machines with ease.

Relay protection in active distribution networks

Increasingly growing share of distributed generation in the whole electrical power system’s generating system is currently a worldwide tendency, driven by several factors, encircling mainly difficulties in refinement of megalopolises’ distribution networks and its maintenance; widening environmental concerns adding to both energy efficiency approaches and installation of renewable sources based generation, inherently distributed; increased power quality and reliability needs; progress in IT field, making implementable harmonization of needs and interests of different-energy-type generators and consumers. At this stage, the volume, formed by system-interconnected distributed generation facilities, have reached the level of causing broad impact toward system operation under emergency and post-emergency conditions in several EU countries, thus previously implementable approach of their preliminary tripping in case of a fault, preventing generating equipment damage and disoperation of relay protection and automation, is not applicable any more. Adding to the preceding, withstand capability and transient electromechanical stability of generating technologies, interconnecting in proximity of load nodes, enhanced significantly since the moment Low Voltage Ride-Through regulations, followed by techniques, were introduced in Grid Codes. Both aspects leads to relay protection and auto-reclosing operation in presence of distributed generation generally connected after grid planning and construction phases. This paper proposes solutions to the emerging need to ensure correct operation of the equipment in question with least possible grid refinements, distinctively for every type of distributed generation technology achieved its technical maturity to date and network’s protection. New generating technologies are equivalented from the perspective of representation in calculation of initial steady-state short-circuit current used to dimension current-sensing relay protection, and widely adopted short-circuit calculation practices, as IEC 60909 and VDE 0102. The phenomenon of unintentional islanding, influencing auto-reclosing, is addressed, and protection schemes used to eliminate an sustained island are listed and characterized by reliability and implementation related factors, whereas also forming a crucial aspect of realization of the proposed protection operation relieving measures.

As definições teóricas de direitos humanos de Jürgen Habermas: o princípio legal e as correções morais[ign] [title language="en"]The theoretical definitions of human rights of Jürgen Habermas[ign]: [subtitle]legal principle and moral corrections

No entendimento de Habermas, "direito", na expressão "direitos humanos", é um conceito jurídico, donde direitos humanos, para ele, serem direitos jurídicos, normas legais declaradas em atos de fundações do Estado ou anunciadas em convenções do direito internacional e/ou constituições estatais. Ao conceber assim os direitos e tematizar os direitos humanos numa abordagem tríplice (focando-os entre moral, direito e política), ele fornece diferentes definições teóricas dos direitos humanos. O texto apresenta uma exposição sistemática dessas definições e focaliza os diferentes problemas que motivaram Habermas a alterar e ampliar suas concepções de direitos humanos.