Avaliação do conhecimento de pacientes de reabilitação cardíaca: Brasil versus Canadá

FUNDAMENTO: Grande parte da relação entre o estado de saúde e o conhecimento sobre saúde e doença pode ser atribuída aos efeitos combinados de comportamento dísparrelacionado à saúde, condições ambientais e estruturas socioeconômicas, bem como o contato com a atenção à saúde e prestação da mesma. OBJETIVO: O objetivo do presente estudo foi descrever e comparar o conhecimento dos pacientes com doença arterial coronariana (DAC),incluídos em programas de reabilitação cardíaca (RC) no Brasil e no Canadá, sobre os fatores relacionados à DAC. MÉTODOS: Duas amostras de 300 pacientes brasileiros e 300 pacientes canadensesincluídos em RC foram comparadas transversalmente. Os pacientes brasileiros foram recrutados de dois centros de RC no Sul do Brasil, enquanto os pacientes canadenses foram recrutados de um centro de RC em Ontário. O conhecimento foi avaliado utilizando o Questionário de Educação de Doença Arterial Coronariana (CADE-Q), psicometricamente validado em Português e Inglês. Os dados foram processados por meio de estatísticas descritivas, post-hoc eteste t de Student. RESULTADOS: A pontuação média total de conhecimento para toda a amostra foi de 41,42 ± 9,3. Os entrevistados canadenses apresentaram pontuações totais de conhecimento significativamente maiores do que os entrevistados brasileiros. O domínio mais bem esclarecido em ambas as amostras foi o exercício físico.Em 13 de 19 questões, os entrevistados canadenses relataram pontuações de conhecimento significativamente maiores do que os entrevistados brasileiros. CONCLUSÃO: Pacientes ambulatoriais canadenses relataram conhecimento significativamente maior que suas contrapartes brasileiras. Os resultados também sugeremque um currículo educacional estruturado em programas de RC pode contribuir para um maior conhecimentodo paciente, o que pode em última análise facilitar as mudanças comportamentais.

Development and implementation of an integrated technical management system

Quality Management, Integrated Technical Management Systems, ITMS, Technical Elements, Environment, Occupational Health and safety, OH&S, Standards, ISO, General Regulations, Integration, Management Functions, Computer Centre, Suc-cess Concepts, Documentation, PCT, QMS, EMS, OH&S-MS, Portioning, Evaluation, Technical Cycle, Technical Compliance, Framework

Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

Estudos citológicos em Hemíoteros da família Coreidae

A more or less detailed study of the spermatogenesis in six species of Hemiptera belonging to the Coreid Family is made in the present paper. The species studied and their respective chromosome numbers were: 1) Diactor bilineatus (Fabr.) : spermatogonia with 20 + X, primary spermatocytes with 10 + X, X dividing equationaliv in the first division and passing undivided to one pole in the second. 2) Lcptoglossus gonagra (Fabr.) : spermatogonia with 20 + X, primary spermatocytes with 10 + X, X dividing equationally in the first division and passing undivided to one pole in the second. 3) Phthia picta (Drury) : spermatogonia with 20 + X, primary spermatocytes with 10 + X, X dividing equationally in the first division and passing undivided to one pole in the second. 4) Anisocelis foliacea Fabr. : spermatogonia with 26 + X fthe highest mumber hitherto known in the Family), primary .spermatocytes with 13 + X, X dividing equationally in the first division an passing undivided to one pole in the second. 5) Pachylis pharaonis (Herbtst) : spermatogonia with 16 + X, primary spermatocytes with 8 + X. Behaviour of the heteroehromosome not referred. 6) Pachylis laticornis (Fabr.) : spermatogonia with 14 + X, primary spermatocytes with 7 + X, X passing undivided to one pole in the first division and therefore secondary spermatocytes with 7 + X and 7 chromosomes. General results and conclusions a) Pairing modus of the chromosomes (Telosynapsis or Farasynapsis ?) - In several species of the Coreld bugs the history of the chromosomes from the diffuse stage till diakinesis cannot be follewed in detail due specially to the fact that lhe bivalents, as soon as they begin to be individually distinct they appear as irregular and extremely lax chromatic areas, which through an obscure process give rise to the diakinesis and then to the metaphase chomosomes. Fortunately I was able to analyse the genesis of the cross-shaped chromosomes, becoming thus convinced that even in the less favorable cases like that of Phthia, in which the crosses develop from four small condensation areas of the diffuse chromosomes, nothing in the process permit to interpret the final results as being due to a previous telosynaptic pairing. In the case of long bivalents formed by two parallel strands intimately united at both endsegments and more or less widely open in the middle (Leptoglossus, Pachylis), I could see that the lateral arms of the crosses originate from condensation centers created by a torsion or bending in the unpaired parts of the chromosomes In the relatively short bivalents the lateral branches of the cross are formed in the middle but in the long ones, whose median opening is sometimes considerable, two asymetrical branches or even two independent crosses may develop in the same pair. These observations put away the idea of an end-to-end pairing of the chromosomes, since if it had occured the lateral arms of the crosses would always be symetrical and median and never more than two. The direct observation of a side- toside pairing of the chromosomal threads at synizesis, is in foil agreement with the complete lack of evidence in favour of telosynapsis. b) Anaphasic bridges and interzonal connections - The chromosomes as they separate from each other in anaphase they remain connected by means of two lateral strands corresponding to the unpaired segmenas observed in the bivalents at the stages preceding metaphase. In the early anaphase the chromosomes again reproduce the form they had in late diafcinesis. The connecting threads which may be thick and intensely coloured are generally curved and sometimes unequal in lenght, one being much longer than the other and forming a loop outwardly. This fact points to a continuous flow of chromosomal substance independently from both chromosomes of the pair rather than to a mechanical stretching of a sticky substance. At the end of anaphase almost all the material which formed the bridges is reduced to two small cones from whose vertices a very fine and pale fibril takes its origin. The interzonal fibres, therefore, may be considered as the remnant of the anaphasic bridges. Abnormal behaviour of the anaphase chromosomes showed to be useful in aiding the interpretation of normal aspects. It has been suggested by Schrader (1944) "that the interzonal is nothing more than a sticky coating of the chromosome which is stretched like mucilage between the daughter chromosomes as they move further and further apart". The paired chromosomes being enclosed in a commom sheath, as they separate they give origin to a tube which becomes more and more stretched. Later the walls of the tube collapse forming in this manner an interzonal element. My observations, however, do not confirm Schrader's tubular theory of interzonal connections. In the aspects seen at anaphase of the primary spermatocytes and described in this paper as chromosomal bridges nothing suggests a tubular structure. There is no doubt that the chromosomes are here connected by two independent strands in the first division of the spermatocytes and by a single one in the second. The manner in which the chromosomes separate supports the idea of transverse divion, leaving little place for another interpretation. c) Ptafanoeomc and chromatoid bodies - The colourabtlity of the plasmosome in Diactor and Anisocelis showed to be highly variable. In the latter species, one may find in the same cyst nuclei provided with two intensely coloured bodies, the larger of which being the plasmosome, sided by those in which only the heterochromosome took the colour. In the former one the plasmosome strongly coloured seen in the primary metaphase may easily be taken for a supernumerary chromosome. At anaphase this body stays motionless in the equator of the cell while the chromosomes are moving toward the poles. There, when intensely coloured ,it may be confused with the heterochromosome of the secondary spermatocytes, which frequently occupies identical position in the corresponding phase, thus causing missinterpretation. In its place the plasmosome may divide into two equal parts or pass undivided to one cell in whose cytoplasm it breaks down giving rise to a few corpuscles of unequal sizes. In Pachylis pharaonis, as soon as the nuclear membrane breate down, the plasmosome migrates to a place in the periphery of the cell (primary spermatocyte), forming there a large chromatoid body. This body is never found in the cytoplasm prior to the dissolution of the nuclear membrane. It is certain that chromatoid bodies of different origin do exist. Here, however, we are dealing, undoubtedly, with true plasmosomes. d) Movement of the heterochromosome - The heterochromosome in the metaphase of the secondary spermatocytes may occupy the most different places. At the time the autosomes prient themselves in the equatorial plane it may be found some distance apart in this plane or in any other plane and even in the subpolar and polar regions. It remains in its place during anaphase. Therefore, it may appear at the same level with the components of one of the anaphase plates (synchronism), between both plates (succession) or between one plate and tbe pole (precession), what depends upon the moment the cell was fixed. This does not mean that the heterochromosome sometimes moves as quickly as the autosomes, sometimes more rapidly and sometimes less. It implies, on the contrary, that, being anywhere in the cell, the heterochromosome m he attained and passed by the autosomes. In spite of being almost motionless the heterochromosome finishes by being enclosed in one of the resulting nuclei. Consequently, it does move rapidly toward the group formed by the autosomes a little before anaphase is ended. This may be understood assuming that the heterochromosome, which do not divide, having almost inactive kinetochore cannot orient itself, giving from wherever it stays, only a weak response to the polar influences. When in the equator it probably do not perform any movement in virtue of receiving equal solicitation from both poles. When in any other plane, despite the greater influence of the nearer pole, the influence of the opposite pole would permit only so a slow movement that the autosomes would soon reach it and then leave it behind. It is only when the cell begins to divide that the heterochromosome, passing to one of the daughter cells scapes the influence of the other and thence goes quickly to join the autosomes, being enclosed with them in the nucleus formed there. The exceptions observed by BORING (1907) together with ; the facts described here must represent the normal behavior of the heterocromosome of the Hemiptera, the greater frequency of succession being the consequence of the more frequent localization of the heterochromosome in the equatorial plane or in its near and of the anaphase rapidity. Due to its position in metaphase the heterochromosome in early anaphase may be found in precession. In late anaphase, oh the contrary ,it appears almost always in succession. This is attributed to the fact of the heterochromosome being ordinairily localized outside the spindle area it leaves the way free to the anaphasic plate moving toward the pole. Moreover, the heterochromosome being a round element approximately of the size of the autosomes, which are equally round or a little longer in the direction of the movement, it can be passed by the autosomes even when it stands in the area of the spindle, specially if it is not too far from the equatorial plane. e) The kinetochore - This question has been fully discussed in another paper (PIZA 1943a). The facts treated here point to the conclusion that the chromosomes of the Coreidae, like those of Tityus bahiensis, are provided with a kinetochore at each end, as was already admitted by the present writer with regard to the heterochromosome of Protenor. Indeed, taking ipr granted the facts presented in this paper, other cannot be the interpretation. However, the reasons by which the chromosomes of the species studied here do not orient themselves at metaphase of the first division in the same way as the heterochromosome of Protenor, that is, with the major axis parallelly to the equatorial plane, are claiming for explanation. But, admiting that the proximity of the kinetochores at the ends of chromosomes which do not separate until the second division making them respond to the poles as if they were a single kinetochore ,the explanation follows. (See PIZA 1943a). The median opening of the diplonemas when they are going to the diffuse stage as well as the reappearance of the bivalents always united at the end-segments and open in the middle is in full agreement with the existence of two terminal kinetochores. The same can be said with regard to the bivalents which join their extremities to form a ring.

Pesquisas sôbre a análise estatística de experiências de adubação com o auxílio da lei de Mitscherlich

Statistical analyses of an experiment on wheat were carried out with the aid of Mitscherlich's law. The experiment was made in Ponta Grossa, Paraná, by the Ministry of Agriculture of Brasil. Lime, in the form of Ca(OH)2, was applied at the levels of 0, 2, 4, 6 and 8 metric tons per hectare. A 5 x 5 Latin square was used. Lime was applied in 1940 and wheat was cultivated in the same plots for several years. The following fertilizers were annually used for all plots: NaNO3 100 kilograms per hectare, Superphosphate 350 kilograms per hectare, K2S04 80 kilograms per hectare. The statistical analysis of the data collected in 1941, 1942, 1943, 1947 and 1948, carried out in accordance with the methods previously introduced by Pimentel Gomes and Malavolta (1949 a, 1949 b) and Pimentel Gomes (1950), proved: I. That Mitscherlich's law could be correctly applied to the data. II. That there was a statistically significant effect of lime on wheat yield. III. That the optimum amount of lime to be applied to the soil lies between 5 and 15 hundred kilograms of Ca(OH)2 per hectare. IV. That there is a migration of calcium from some plots to others, in such a way that the data obtained in 1947 and 1948 are not representative of the amounts of lime applied in 1940. V. That the analysis of variance can be used, as the Bartlett test shows that the variances at the distinct levele of lime application are not statistically different. It must be noted that, with improved variety and fertilization, the yield was rised to about 2500 kilograms per hectare in 1947, and 1600 in 1948, being only of about 100 kilograms per hectare in 1940.

Biologia da Arsenura xanthopus (Walker, 1855) ( Lepidoptera - Adelocephalidae ), praga do «Açoita-Cavalo» (Luehea spp.) e notas sôbre seus inimigos naturais

Biology of Arsenura xanthopus (Walker, 1855) (Lep., Adelocephalidae), a pest of Luehea spp. (Tiliaceae), and notes on its natural enemies. In the beginning of 1950, one of the Authors made some observations about the biology of Arsenura xanthopus (Walker), in Piracicaba, State of S. Paulo, Brazil. From 1951 to 1953, both Authors continued the observations on such an important Adelocephalidae, the caterpillars of which represent a serious pest of Luehea spp. leaves. Actually, in some occasions, the caterpillars can destroy completely the leaves of the trees. The species is efficientely controlled by two natural enemies: an egg parasite (Tetrastichus sp., Hym., Eulophidae) and a fly attacking the last instar caterpillar (Winthemia tricolor (van der Wulp), Dip., Tachinidae). Tetrastichus sp. can destroy 100% of the eggs and the fly, 70 to 100% of the caterpillars. Indeed, facts as such are very interesting because we rarely know of a case of so complete a control of a pest by an insect. A. xanthopus had not yet been mentioned in our literature. Actually neither the systematic bibliography nor the economic one has treated of this species. However, a few other species of Arsenura are already known as living on Luehea spp. According to the Authors' observations, W. tricolor was also unknown by the Brazilian entomological literature. Arsenura xanthopus (Walker, 1855) After giving the sinonimy and a few historical data concerning the species, and its geographical distribution, the Authors discuss its placing in the genus Arsenura Duncan or Rhescyntis Huebner, finishing by considering Arsenura xanthopus as a valid name. The Authors put the species in the family Adelocephalidae, as it has been made by several entomologists. The host plant The species of Tiliaceae plants belonging to the genus Luehea are called "açoita-cavalo" and are well known for the usefulness of their largely utilized wood. The genus comprises exclusively American plants, including about 25 species distributed throughout the Latin America. Luehea divaricata Mart, is the best known species and the most commonly cultivated. Biology of Arsenura xanthopus Our observations show that the species passes by 6 larval stages. Eggs and egg-postures, all the 6 instars of the caterpillars as well as the chrysalid are described. The pupal period is the longest of the cycle, taking from 146 to 256 days. Data on the eclosion and habits of the caterpillars are also presented. A redescription of the adult is also given. Our specimens agreed with BOUVIER's description, except in the dimension between the extremities of the extended wings, which is a little shorter (107 mm according to BOUVlErVs paper against from 80 to 100mm in our individuals). Winthemia tricolor (van der Wulp, 1890) Historical data, geographical distribution and host are first related. W. tricolor had as yet a single known host-; Ar^-senura armida (Cramer). This chapter also contains some observations on the biolcn gy of the fly and on its behaviour when trying to lay eggs on the caterpillars' skin. The female of W. tricolor lays from 1 to 33 eggs on the skin of the last instar caterpillar. The mam region of the body where the eggs are laid are the membranous legs. Eggs are also very numerous oh the ventral surface of the thorax and abdomen. The. preference for such regions is easily cleared up considering the position assumed by the caterpillar when fixed motionless in a branch. In such an occasion, the fly approaches, the victim, puts the ovipositor out and lays the eggs on different parts of the body, mainly on the mentioned regions, which are much more easily reached. The eggs of the fly are firmly attached to the host's skin, being almost impossible to detach them, without having them broken. The minute larvae of the fly enter the body of, the host when it transforms into chrysalid. Chrysalids recentely formed and collected in nature f requentely show a few small larvae walking on its skin and looking for an adequate place to get into the body. A few larvae die by remaining in the skin of the caterpillar which is pushed away to some distance by the active movements of the chrysalid recentely formed. From 1 to 10 larvae completely grown may emerge from the attacked chrysalid about 8 days after their penetrating into the caterpillars' body and soon begin to look for an adequate substratum where they can transform themselves into pupae. In natural conditions, the metamorphosis occurs in the soil. The flies appear within 15 days. Tetrastichus sp. This microhymenoptera is economically the most interesting parasite, being commonly able to destroy the whole pos^ ture of the moth. Indeed, some days after the beginning of the infestation of the trees, it is almost impossible to obtain postures completely free of parasites. The active wasp introduces the ovipositor into the egg of the moth, laying its egg inside, from 80 to 120 seconds after having introduced it. A single adult wasp emerges from each egg. Sarcophaga lambens Wiedemann, 1830 During the observations carried out, the Authors obtained 10 flies from a chysalid that were recognized as belonging to the species above. S. lambens is a widely distributed Sarcophagidae, having a long list of hosts. It is commonly obtained from weak or died invertebrates, having no importance as one of their natural enemies. Sinonimy, list of hosts and distribution are presented in this paper. Control of Arsenura xanthopus A test has been carefully made in the laboratory just to find out the best insecticide for controlling A. xanthopus caterpillars. Four different products were experimented (DDT, Pa-rathion, BHC and Fenatox), the best results having been obtained with DDT at 0,25%. However, the Authors believe in spite of the initial damages of the trees, that the application of an insecticide may be harmful by destroying the natural agents of control. A biological desiquilibrium may in this way take place. The introduction of the parasites studied (Tetrastichus sp. and Winthemia tricolor) seems to be the most desirable measure to fight A. xanthopus.

Determinação de potássio em fertilizantes por fotometria de chama

O presente trabalho relata um estudo sobre a determinação do potássio em fertilizantes por fotometria de chama e empregando o aparelho Coleman, modêlo 21. A precisão do método foi estudada, aplicando-o na análise de 3misturas contendo os fertilizantes sulfato de amônio e superfosfato simples ou triplo e uma quantidade conhecida de potássio na forma de sal puro, para análise (KC1 p.a.). As determinações do potássio foram executadas nas soluções das mencionadas misturas, após eliminar os ânions sulfato e fosfato com a resina Amberlite IR-4B (OH). Os dados obtidos evidenciaram que o método em questão além de ser muito rápido, forneceu resultados satisfatórios, quando se consideram as diluições necessárias para as determinações. Outras determinações executadas simultaneamente, e em soluções das mesmas misturas, mas sem eliminar os ânions sulfato e fosfato, forneceram dados próximos aos obtidos com a eliminação dos citados ânions.

Efeito da adição de uréia e sulfato de amônio sobre o pH e nitrificação em um solo ácido

A variação do pH e a produção de nitrato foram estudados em um Latossolo Vermelho Escuro, Série Guamium, em função da adição de 200 e 400 ppm de N nas formas de uréia e sulfato de amônio, em presença e ausência de Ca(OH)2 por um período de 30 dias. Os resultados obtidos mostraram que o pH decresceu com o sulfato de amônio e aumentou com a uréia. As variações foram observadas mesmo empresença de Ca(0H)2. A produção de nitrato aumentou com o pH, considerando o mesmo nível e fonte de nitrogênio. Não foi observado no conjunto uma relação entre pH e produção de nitrato.

Sobre um método de concentração de enterovírus em água de esgoto pelo hidróxido de alumínio

O presente trabalho descreve um estudo experimental em que foi testada a eficiência de um método para concentração de enterovírus em água de esgoto por adsorção ao hidróxido de alumínio. Adicionou-se o gel de A1 (OH)3 (na proporção de 1g para 3,78 litros) à água de esgoto previamente clarificada e com o pH acertado em 5,0. Depois de agitada por 1 hora, a mistura foi filtrada em membrana Millipore tipo AP-20. O hidróxido de alumínio, o qual permaneceu retido na membrana, foi retirado com auxílio de uma espátula e a ele se adicionou meio de Eagle com 10% de soro fetal, sendo o pH acertado em torno de 7,2 - 7,4 para se processar a eluição. A mistura foi centrifugada a 20.000g por 15 minutos, o sedimento desprezado e o sobrenadante inoculado em células da linhagem LLC-MK2 para quantificação viral. Paralelamente, foram também inoculadas em cultura de células as amostras de esgoto brutas, isto é, antes de qualquer procedimento para concentração. O método descrito se mostrou eficiente para concentrar enterovírus em água de esgoto, sendo que tornou possível detectar vírus mesmo de amostras contendo cerca de 1 unidade infecciosa por ml, das quais não se conseguiu isolamento de vírus sem concentração prévia.

On the adjuvant effect of aluminum hydroxide for mice

Linear relationships were found between the dose of A1(OH)3 adjuvant and the titer of anti-OVA antibodies formed by BDF1 mice. Mice immunized with OVA, DNP-KLH and then boosted with DNP-OVA formed anti-DNP antibodies only when A1(OH)3 was added to the injection of DNP-KLH; addition of A1(OH)3 to the priming injection of OVA decreased, rather than increased antibody formation.

Effect of vitamin D on Epstein-Barr (EBV)-specific CD8+T cells in patients with early multiple sclerosis (MS)

Background: Infection with EBV and a lack in vitamin D may be important environmental triggers of MS. 1,25-(OH)2D3 mediates a shift of antigen presenting cells (APC) and CD4+ T cells to a less inflammatory profile. Although CD8+ T cells do express the vitamin D receptor, a direct effect of 1,25(OH)2D3 on these cells has not been demonstrated until now. Since CD8+ T cells are important immune mediators of the inflammatory response in MS, we examined whether vitamin D directly affects the CD8+ T cell response, and more specifically if it modulates the EBV-specific CD8+ T cell response. Material and Methods: To explore whether the vitamin D status may influence the pattern of the EBV-specific CD8+ T cell response, PBMC of 10 patients with early MS and 10 healthy controls (HC) were stimulated with a pool of immunodominant 8-10 mer peptide epitopes known to elicit CD8+ T cell responses. PBMC were stimulated with this EBV CD8 peptide pool, medium (negative control) or anti- CD3/anti-CD28 beads (positive control). The following assays were performed: ELISPOT to assess the secretion of IFN-gamma by T cells in general; cytometric beads array (CBA) and ELISA to determine whichcytokines were released by EBV-specific CD8+ T cells after six days of culture; and intracellular cytokine staining assay to determine by which subtype of T cells secreted given cytokines. To examine whether vitamin D could directly modulate CD8+ T cell immune responses, we depleted CD4+ T cells using negative selection. Results: We found that pre-treatment of vitamin D had an antiinflammatory action on both EBV-specific CD8+ T cells and on CD3/ CD28-stimulated T cells: secretion of pro-inflammatory cytokines (IFNgamma and TNF-alpha) was decreased, whereas secretion of antiinflammatory cytokines (IL-5 and TGF-beta) was increased. At baseline, CD8+ T cells of early MS patients showed a higher secretion of TNFalpha and lower secretion of IL-5. Addition of vitamin D did not restore the same levels of both cytokines as compared to HC. Vitamin D-pretreated CD8+T cells exhibited a decreased secretion of IFN-gamma and TNF-alpha, even after depletion of CD4+ T cells from culture. Conclusion: Vitamin D has a direct anti-inflammatory effect on CD8+ T cells independently from CD4+ T cells. CD8+ T cells of patients with earlyMS are less responsive to the inflammatory effect of vitamin D than HC, pointing toward an intrinsic dysregulation of CD8+ T cells. The modulation of EBV-specific CD8+T cells by vitaminDsuggests that there may be interplay between these twomajor environmental factors of MS. This study was supported by a grant from the Swiss National Foundation (PP00P3-124893), and by an unrestricted research grant from Bayer to RDP.

Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy

BACKGROUND: Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in patients with chronic hepatitis C. We therefore performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms within the vitamin D cascade on chronic hepatitis C and its treatment. METHODS: Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and the 1α- hydroxylase were determined in a cohort of 468 HCV genotype 1, 2 and 3 infected patients who were treated with interferon-alfa based regimens. RESULTS: Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D3<10 ng/mL in 25% versus 12%, p<0.00001), which was in part reversible after HCV eradication. 25(OH)D3 deficiency correlated with SVR in HCV genotype 2 and 3 patients (63% and 83% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.001). In addition, the CYPB27-1260 promoter polymorphism rs10877012 had substantial impact on 1-25- dihydroxyvitamin D serum levels and SVR rates in HCV genotype 1, 2 and 3 infected patients. CONCLUSIONS: Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25- hydroxyvitamin D levels and CYPB27-1260 promoter polymorphism are associated with failure to achieve SVR in HCV genotype 1, 2, 3 infected patients.

High prevalence of hypovitaminosis D in a Swiss rheumatology outpatient population.

Vitamin D is important for bone metabolism and neuromuscular function. While a routine dosage is often proposed in osteoporotic patients, it is not so evident in rheumatology outpatients where it has been shown that the prevalence of hypovitaminosis D is high. The aim of the current study was to systematically evaluate the vitamin D status in our outpatient rheumatology population to define the severity of the problem according to rheumatologic diseases. During November 2009, all patients were offered a screening test for 25-OH vitamin D levels and categorised as deficient (<10 µg/l [ng/ml] [25 nmol/l]), insufficient (10 µg/l to 30 µg/l [25 to 75 nmol/l]) or normal (>30 µg/l [75 nmol/l]). A total of 272 patients were included. The mean 25-OH vitamin D level was 21 µg/l (range 1.5 to 45.9). A total of 20 patients had vitamin D deficiency, 215 patients had an insufficiency and 37 patients had normal results. In the group of patients with osteoporosis mean level of 25-OH vitamin D was 25 µg/l and 31% had normal results. In patients with inflammatory rheumatic diseases (N = 219), the mean level of 25-OH vitamin D was 20.5 µg/l, and only 12% had normal 25-OH vitamin D levels. In the small group of patients with degenerative disease (N = 33), the mean level of 25-OH vitamin D was 21.8 µg/l, and 21% had normal results. Insufficiency and deficiency were even seen in 38% of the patients who were taking supplements. These results confirm that hypovitaminosis D is highly prevalent in an outpatient population of rheumatology patients, affecting 86% of subjects. Despite oral supplementation (taken in 38% of our population), only a quarter of those on oral supplementation attained normal values of 25-OH vitamin D.

Chirality in the new generation of antidepressants: stereoselective analysis of the enantiomers of mirtazapine, N-demethylmirtazapine, and 8-hydroxymirtazapine by LC-MS.

Mirtazapine is an antidepressant that acts specifically on noradrenergic and sertonergic receptors. A LC-MS method was developed that allows the simultaneous analysis of the R-(-)- and S-(+)-enantiomers of mirtazapine (MIR), demethylmirtazapine (DMIR), and 8-hydroxymirtazapine (8-OH-MIR) in plasma of MIR-treated patients. The method involves a 3-step liquid-liquid extraction, an HPLC separation on a Chirobiotic V column, and MS detection in electrospray mode. The limit of quantification (LOQ) for all enantiomers was 0.5 ng/mL, and the intra- and interday CVs were within 3.3% to 11.7% (concentration ranges 5-50 ng/mL). A method is also presented for the quantitative analysis of glucuroconjugated MIR and 8-OH-MIR. S-(+)-8-OH-MIR is present in plasma mainly as its glucuronide. Preliminary data suggest that in all patients, except in those comedicated with CYP2D6 inhibitors such as fluoxetine and thioridazine, R-(-)-MIR concentrations were higher than those of S-(+)MIR. Moreover, fluvoxamine seems also to inhibit the metabolism of MIR. Therefore, this method seems to be suitable for the stereoselective assay of MIR and its metabolites in plasma of patients comedicated with MIR and other drugs for routine and research purposes.