Desempenho e perfil hematol��gico da T��l��pia-do-Nilo alimentada com dietas suplementadas com ferro e cobre e submetida ao estresse por calor

Coordena����o de Aperfei��oamento de Pessoal de N��vel Superior (CAPES)

Suplementa����o diet��ria de cobre no desempenho produtivo da til��pia-do-Nilo e resposta hem��tica sob estresse t��rmico

P��s-gradua����o em Zootecnia - FMVZ

Avalia����o do crescimento e da atividade imune de til��pias alimentadas com dietas suplementadas com unha de gato (Uncaria tomentosa)

P��s-gradua����o em Aquicultura - FCAV

Efeito da inocula����o via esof��gica de microbiota intestinal�� sobre a hematologia, desenvolvimento e integridade intestinal de pintos de corte

Conselho Nacional de Desenvolvimento Cient��fico e Tecnol��gico (CNPq)

Respostas fisiol��gicas do matrinx�� Brycon amazonicus ap��s mudan��a de ambientes com diferentes concentra����es de sais de c��lcio e de s��dio

Coordena����o de Aperfei��oamento de Pessoal de N��vel Superior (CAPES)

Toxicidade do sulfato de cobre para a til��pia, Oreochromis niloticus e teste ecotoxicol��gico com Ceriodaphnia d��bia e Pseudokirchneriella subcapitata

Coordena����o de Aperfei��oamento de Pessoal de N��vel Superior (CAPES)

N��veis de prote��na e energia digest��veis para til��pia-do-nilo criada em tanques-rede na fase de termina����o

P��s-gradua����o em Zootecnia - FMVZ

Zearalenone, an estrogenic mycotoxin, is an immunotoxic compound

The aim of this study was to assess the toxic effects of zearalenone (ZEA) on the immune function. Ovariectomised rats were treated daily by gavage with 3.0 mg/kg of ZEA for 28 days. Body weight gain, food consumption, haemotological parameters, lymphoid organs, and their cellularities were evaluated. Moreover, acquired immune responses and macrophage activity were also assessed. ZEA promoted reduction in body weight gain, which is not fully explained by diminished food consumption. Despite no effect on haematological parameters, ZEA caused thymic atrophy with histological and thymocyte phenotype changes and decrease in the B cell percentage in the spleen. With respect to acquired and innate immune responses, no statistically significant differences in delayed-type hypersensitivity were noticed; however, in the ZEA-treated rats, antibody production and peroxide release by macrophages were impaired. The observed results could be related to ZEA activity on ERs; thus, ZEA is an immunotoxic compound similar to estrogen and some endocrine disruptors.

The Integrated European Project "GEHA - GEnetics of Healthy Aging": recruitment, health status assessment and survival of the Italian 90+ sibpairs

The present study is part of the EU Integrated Project ���GEHA ��� Genetics of Healthy Aging��� (Franceschi C et al., Ann N Y Acad Sci. 1100: 21-45, 2007), whose aim is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced age in good cognitive and physical function and in the absence of major age-related diseases. Aims The major aims of this thesis were the following: 1. to outline the recruitment procedure of 90+ Italian siblings performed by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The procedures related to the following items necessary to perform the study were described and commented: identification of the eligible area for recruitment, demographic aspects related to the need of getting census lists of 90+siblings, mail and phone contact with 90+ subjects and their families, bioethics aspects of the whole procedure, standardization of the recruitment methodology and set-up of a detailed flow chart to be followed by the European recruitment centres (obtainment of the informed consent form, anonimization of data by using a special code, how to perform the interview, how to collect the blood, how to enter data in the GEHA Phenotypic Data Base hosted at Odense). 2. to provide an overview of the phenotypic characteristics of 90+ Italian siblings recruited by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The following items were addressed: socio-demographic characteristics, health status, cognitive assessment, physical conditions (handgrip strength test, chair-stand test, physical ability including ADL, vision and hearing ability, movement ability and doing light housework), life-style information (smoking and drinking habits) and subjective well-being (attitude towards life). Moreover, haematological parameters collected in the 90+ sibpairs as optional parameters by the Bologna and Rome recruiting units were used for a more comprehensive evaluation of the results obtained using the above mentioned phenotypic characteristics reported in the GEHA questionnaire. 3. to assess 90+ Italian siblings as far as their health/functional status is concerned on the basis of three classification methods proposed in previous studies on centenarians, which are based on: ��� actual functional capabilities (ADL, SMMSE, visual and hearing abilities) (Gondo et al., J Gerontol. 61A (3): 305-310, 2006); ��� actual functional capabilities and morbidity (ADL, ability to walk, SMMSE, presence of cancer, ictus, renal failure, anaemia, and liver diseases) (Franceschi et al., Aging Clin Exp Res, 12:77-84, 2000); ��� retrospectively collected data about past history of morbidity and age of disease onset (hypertension, heart disease, diabetes, stroke, cancer, osteopororis, neurological diseases, chronic obstructive pulmonary disease and ocular diseases) (Evert et al., J Gerontol A Biol Sci Med Sci. 58A (3): 232-237, 2003). Firstly these available models to define the health status of long-living subjects were applied to the sample and, since the classifications by Gondo and Franceschi are both based on the present functional status, they were compared in order to better recognize the healthy aging phenotype and to identify the best group of 90+ subjects out of the entire studied population. 4. to investigate the concordance of health and functional status among 90+ siblings in order to divide sibpairs in three categories: the best (both sibs are in good shape), the worst (both sibs are in bad shape) and an intermediate group (one sib is in good shape and the other is in bad shape). Moreover, the evaluation wanted to discover which variables are concordant among siblings; thus, concordant variables could be considered as familiar variables (determined by the environment or by genetics). 5. to perform a survival analysis by using mortality data at 1st January 2009 from the follow-up as the main outcome and selected functional and clinical parameters as explanatory variables. Methods A total of 765 90+ Italian subjects recruited by UNIBO (549 90+ siblings, belonging to 258 families) and ISS (216 90+ siblings, belonging to 106 families) recruiting units are included in the analysis. Each subject was interviewed according to a standardized questionnaire, comprising extensively utilized questions that have been validated in previous European studies on elderly subjects and covering demographic information, life style, living conditions, cognitive status (SMMSE), mood, health status and anthropometric measurements. Moreover, subjects were asked to perform some physical tests (Hand Grip Strength test and Chair Standing test) and a sample of about 24 mL of blood was collected and then processed according to a common protocol for the preparation and storage of DNA aliquots. Results From the analysis the main findings are the following: - a standardized protocol to assess cognitive status, physical performances and health status of European nonagenarian subjects was set up, in respect to ethical requirements, and it is available as a reference for other studies in this field; - GEHA families are enriched in long-living members and extreme survival, and represent an appropriate model for the identification of genes involved in healthy aging and longevity; - two simplified sets of criteria to classify 90+ sibling according to their health status were proposed, as operational tools for distinguishing healthy from non healthy subjects; - cognitive and functional parameters have a major role in categorizing 90+ siblings for the health status; - parameters such as education and good physical abilities (500 metres walking ability, going up and down the stairs ability, high scores at hand grip and chair stand tests) are associated with a good health status (defined as ���cognitive unimpairment and absence of disability���); - male nonagenarians show a more homogeneous phenotype than females, and, though far fewer in number, tend to be healthier than females; - in males the good health status is not protective for survival, confirming the male-female health survival paradox; - survival after age 90 was dependent mainly on intact cognitive status and absence of functional disabilities; - haemoglobin and creatinine levels are both associated with longevity; - the most concordant items among 90+ siblings are related to the functional status, indicating that they contain a familiar component. It is still to be investigated at what level this familiar component is determined by genetics or by environment or by the interaction between genetics, environment and chance (and at what level). Conclusions In conclusion, we could state that this study, in accordance with the main objectives of the whole GEHA project, represents one of the first attempt to identify the biological and non biological determinants of successful/unsuccessful aging and longevity. Here, the analysis was performed on 90+ siblings recruited in Northern and Central Italy and it could be used as a reference for others studies in this field on Italian population. Moreover, it contributed to the definition of ���successful��� and ���unsuccessful��� aging and categorising a very large cohort of our most elderly subjects into ���successful��� and ���unsuccessful��� groups provided an unrivalled opportunity to detect some of the basic genetic/molecular mechanisms which underpin good health as opposed to chronic disability. Discoveries in the topic of the biological determinants of healthy aging represent a real possibility to identify new markers to be utilized for the identification of subgroups of old European citizens having a higher risk to develop age-related diseases and disabilities and to direct major preventive medicine strategies for the new epidemic of chronic disease in the 21st century.

Evolution and treatment of vitamin B12 deficiency as a risk factor for (cognitive and functional) neurodegenerative diseases in institutionalized elderly = Evoluci��n y tratamiento de la deficiencia de vitamina B12 como factor de riesgo de enfermedades neurodegenerativas (cognitivas y funcionales) en las personas mayores institucionalizadas.

Prevalence of vitamin B12 deficiency is very common in elderly people and can reach values as high as 40.5% of the population. It can be the result of the interaction among several factors. Vitamin B12 deficiencies have been associated with neurological, cognitive deterioration, haematological abnormalities and cardiovascular diseases that have an important influence on the health of the elderly and their quality of life. It is necessary to approach the problems arisen from the lack of data relative to them. The main objective of this thesis was to analyse the evolution of vitamin B12 status and related parameters, lipid and haematological profiles and their relationship to health risk factors, and to functional and cognitive status over one year and to determine the effect of an oral supplementation of 500 ��g of cyanocobalamin for a short period of 28 days. An additional objective was to analyze the possible effects of medicine intakes on vitamin B status. Three studies were performed: a) a one year longitudinal follow-up with four measure points; b) an intervention study providing an oral liquid supplement of 500 ��g of cyanocobalamin for a 28 days period; and c) analysis of the possible effect of medication intake on vitamin B status using the ATC classification of medicines. The participants for these studies were recruited from nursing homes for the elderly in the Region of Madrid. Sixty elders (mean age 84 _ 7y, 19 men and 41 women) were recruited for Study I and 64 elders (mean age 82 _ 7y, 24 men and 40 women) for Study II. For Study III, baseline data from the initially recruited participants of the first two studies were used. An informed consent was obtained from all participants or their mentors. The studies were approved by the Ethical Committee of the University of Granada. Blood samples were obtained at each examination date and were analyzed for serum cobalamin, holoTC, serum and RBC folate and total homocysteine according to laboratory standard procedures. The haematological parameters analyzed were haematocrit, haemoglobin and MCV. For the lipid profile TG, total cholesterol, LDL- and HDLcholesterol were analyzed. Anthropometric measures (BMI, skinfolds [triceps and subscapular], waist girth and waist to hip ratio), functional tests (hand grip, arm and leg strength tests, static balance) and MMSE were obtained or administered by trained personal. The vitamin B12 supplement of Study II was administered with breakfast and the medication intake was taken from the residents��� anamnesis. Data were analyzed by parametric and non-parametric statistics depending on the obtained data. Comparisons were done using the appropriate ANOVAs or non-parametric tests. Pearsons��� partial correlations with the variable ���time��� as control were used to define the association of the analyzed parameters. XIII The results showed that: A) Over one year, in relationship to vitamin B status, serum cobalamin decreased, serum folate and mean corpuscular volumen increased significantly and total homocysteine concentrations were stable. Regarding blood lipid profile, triglycerides increased and HDL-cholesterol decreased significantly. Regarding selected anthropometric measurements, waist circumference increased significantly. No significant changes were observed for the rest of parameters. B) Prevalence of hyperhomocysteinemia was high in the elderly studied, ranging from 60% to 90 % over the year depending on the cut-off used for the classification. LDL-cholesterol values were high, especially among women, and showed a tendency to increase over the year. Results of the balance test showed a deficiency and a tendency to decrease; this indicates that the population studied is at high risk for falls. Lower extremity muscular function was deficient and showed a tendency to decrease. A highly significant relationship was observed between the skinfold of the triceps and blood lipid profile. C) Low cobalamin concentrations correlated significantly with low MMSE scores in the elderly studied. No correlations were observed between vitamin B12 status and functional parameters. D) Regarding vitamin B12 status, holo-transcobalamin seems to be more sensitive for diagnosis; 5-10% of the elderly had a deficiency using serum cobalamin as a criterion, and 45-52% had a deficiency when using serum holotranscobalamin as a criterion. E) 500 ��g of cyanocobalamin administered orally during 28 days significantly improved vitamin B12 status and significantly decreased total homocysteine concentrations in institutionalized elderly. No effect of the intervention was observed on functional and cognitive parameters. F) The relative change (%) of improvement of vitamin B12 status was higher when using serum holo-transcobalamin as a criterion than serum cobalamin. G) Antiaenemic drug intake normalized cobalamin, urologic drugs and corticosteroids serum folate, and psychoanaleptics holo-transcobalamin levels. Drugs treating pulmonary obstruction increased total homocysteine concentration significantly. H) The daily mean drug intake was 5.1. Fiftynine percent of the elderly took medication belonging to 5 or more different ATC groups. The most prevalent were psycholeptic (53%), antiacid (53%) and antithrombotic (47%) drugs.

An��lisis de la estructura del juego y par��metros morfol��gicos y fisiol��gicos en b��dminton

En este trabajo se ha realizado un an��lisis de la estructura del juego y de los par��metros morfol��gicos y fisiol��gicos en jugadores de b��dminton. Para ello se han realizado 4 estudios aplicados. Objetivo: Los objetivos del trabajo han sido: (1) comprobar si existen diferencias entre el lado dominante y no dominante de las medidas antropom��tricas en jugadores de b��dminton de m��ximo nivel nacional, as�� como verificar si el lado del cuerpo donde se realiza la medici��n puede influir en el c��lculo de la composici��n corporal y del somatotipo. (2) Comparar la estuctura temporal y notacional en partidos de individual masculino entre los Juegos Ol��mpicos de Pek��n y de Londres para observar como ha evolucionado el b��dminton de 2008 a 2012. (3) Medir la ocurrencia de da��o muscular despu��s de un partido simulado de b��dminton y su influencia en par��metros f��sicos y hematol��gicos. (4) Investigar la efectividad de una bebida energ��tica que contiene cafe��na para mejorar el rendimiento f��sico y el rendimiento en un partido en jugadores de ��lite de b��dminton. Metodolog��a: Para caracterizar el b��dminton participaron en esta tesis un total de 78 jugadores de b��dminton de ��lite (63 hombres y 15 mujeres), distribuidos en tres estudios y se analizaron 40 sets de b��dminton de individual masculino usando los videos oficiales de los Juegos Ol��mpicos de Pek��n 2008 y Londres 2012. En el primer estudio se tomaron medidas de pliegues cut��neos, di��metros, longitudes y per��metros del lado dominante y no dominante de los jugadores. Se calcul�� la composici��n corporal y el somatotipo. En el segundo estudio se analizaron los factores temporales y los factores notacionales de los partidos. En el tercer estudio se midieron la fuerza m��xima isom��trica, la velocidad en test espec��ficos de b��dminton y se tomaron muestras de sangre antes y despu��s de jugar un partido de b��dminton de 45 minutos. En el cuarto estudio se realiz�� un experimento a doble ciego, aleatorizado y controlado con placebo, los jugadores ingirieron 3 mg de cafe��na por kil��gramo de masa corporal en forma de bebida energ��tica, o la misma bebida sin cafe��na (placebo). En este estudio se registraron diferente tests espec��ficos de b��dminton (tests de salto, fuerza m��xima y test de agilidad) y se jug�� un partido simulado de 45 minutos. Resultados y discusi��n: (1) El porcentaje ��seo fue mayor calculado a partir de las mediciones del lado dominante (dominante = 16.37 �� 1.14 %, no dominante = 15.66 �� 1.12 %; P < 0.001), mientras que el porcentaje muscular fue mayor calculado a partir de las mediciones del lado no dominante (dominante = 49.39 �� 2.60 %, no dominante = 50.18 �� 2.69%; P < 0.001). (2) La duraci��n del set (Pek��n: 1124.6 �� 229.9 s vs Londres: 1260.3 �� 267.1 s.; P < 0.05), el tiempo real de juego (Pek��n: 306.9 �� 45.7 s vs Londres: 354.7 �� 86.5 s; P < 0.05), tiempo de rally, golpeos por rally, tiempo de descanso en el punto 11, tiempo de descanso entre sets y golpeos por rally fueron significativamente mayores en Londres que en Pek��n. (3) El partido simulado de b��dminton no afect�� a la fuerza isom��trica m��xima (Pre: 1263.6 �� 245.5, Post: 1290.8 �� 240.4 N) o a la velocidad espec��fica de b��dminton (Pre: 21.0 �� 1.7, Post: 20.9 �� 1.8 s), sin embargo las concentraciones de mioglobina y de creatina quinasa en sangre aumentaron de 26.5 �� 11.6 a 197.3 �� 70.2 ��g ��� L-1 y de 258.6 �� 192.2 a 466.0 �� 296.5 U ��� L-1, respectivamente despu��s del partido de b��dminton. (4) En comparaci��n con la bebida placebo, la ingesta de la bebida energ��tica con cafe��na increment�� la altura del SJ (34.5��4.7 vs. 36.4��4.3 cm; P < 0.05) y del CMJ (37.7 �� 4.5 vs. 39.5 �� 5.1 cm; P < 0.05) y aument�� el n��mero de aceleraciones totales durante el partido (7395 �� 1594 vs. 7707 �� 2033 aceleraciones; P < 0.05). Conclusiones: (1) Existen asimetr��as corporales en los jugadores de b��dminton de alto nivel, al encontrarse diferencias en los di��metros ��seos y en los per��metros entre el lado dominante y no dominante. Al calcular la composici��n corporal con el lado dominante de los jugadores de b��dminton se est�� sobreestimando el porcentaje ��seo e infraestimando el porcentaje muscular. (2) El b��dminton est�� evolucionando hac��a rallies m��s largos con intervalos de descanso mayores, lo que resulta en partidos m��s largos. (3) El partido de b��dminton gener�� da��o muscular, sin embargo, el nivel de da��o muscular alcanzado despu��s de un partido de b��dminton no produjo una disminuci��n del rendimiento muscular. (4) El uso de una bebida energ��tica con cafe��na puede ser una ayuda nutricional eficaz para aumentar el rendimiento en el salto y patrones de actividad durante el juego en jugadores de ��lite de b��dminton. ABSTRACT: This study analyzes the structure of the game and the morphological and physiological parameters in badminton players, investigated in four applied studies. Purpose: The purposes of the study were: (1) To check if there are differences between the dominant and non-dominant side in the anthropometric measures of badminton players at the highest national level and verify if the side of the body where the measurements are performed can influence the calculation of the body composition and the somatotype. (2) To compare the temporal and notational structure in men���s singles matches between the Olympic Games in Beijing and London to observe the evolution of badminton between 2008 and 2012. (3) To asses the occurrence of muscle damage after a simulated badminton match and its influence on physical and haematological parameters. (4) To determine the effectiveness of a commercially available energy drink that contains caffeine to improve match performance in elite badminton players. Methods: A total of 78 elite badminton players (63 men and 15 women) participated in this thesis to characterize the sport of badminton distributed in three studies and 40 sets of men���s singles badminton analyzed using the official videos of the Olympic Games of Beijing 2008 and London 2012. In the first study skinfolds, diameters, lengths and perimeters of the dominant and non-dominant side of the players were measured and body composition and somatotype were calculated. In the second study the temporal and notational factors were analyzed. In the third study maximal isometric force and speed in badminton specific tests were measured and blood samples were taken before and after a badminton match of 45 minutes. In the fourth study, a double-blind, randomized placebo-controlled experiment, players ingested 3 mg of caffeine per kilogram of body mass in the form of an energy drink or an identical drink with no caffeine content (placebo). In this study different badminton specific tests (jump tests, handgrip force test and an agility test) were recorded and a simulated badminton match of 45 minutes was played. Results and discussion: (1) The percentage of bone was higher when calculated from measurements of the dominant body side (dominant = 16.37 �� 1.14 %, nondominant = 15.66 �� 1.12 %; P < 0.001), while the muscle percentage was higher when calculated from measurements of the non-dominant side (dominant = 49.39 �� 2.60 %, non-dominant = 50.18 �� 2.69%; P < 0.001). (2) Set duration (Beijing: 1124.6 �� 229.9 s vs. London: 1260.3 �� 267.1 s.; P < 0.05), real time played (Beijing: 306.9 �� 45.7 s vs. London: 354.7 �� 86.5 s; P < 0.05), rally time, shots per rally, rest time at point 11, rest time between sets and shots per rally were significantly higher in London than in Beijing. (3) A simulated badminton match did not affect maximal isometric force (Pre: 1263.6 �� 245.5, Post: 1290.8 �� 240.4 N) or specific badminton speed (Pre: 21.0 �� 1.7, Post: 20.9 �� 1.8 s), however, concentrations of myoglobin and creatine kinase in blood increased from 26.5 �� 11.6 to 197.3 �� 70.2 ��g ��� L-1 and from 258.6 �� 192.2 to 466.0 �� 296.5 U ��� L-1, respectively after the badminton match. (4) In comparison to the placebo drink, the caffeinated beverage increased height in the SJ (34.5��4.7 vs. 36.4��4.3 cm; P < 0.05) and in the CMJ (37.7 �� 4.5 vs. 39.5 �� 5.1 cm; P < 0.05) and increased the number of total accelerations during the match (7395 �� 1594 vs. 7707 �� 2033 accelerations; P < 0.05). Conclusions: (1) Body asymmetries were found in high level badminton players, due to the differences found in bone diameters and perimeters between the dominant and non-dominant body side. When calculating body composition with the dominant side of the badminton players we are overestimating bone percentage and underestimating muscle percentage. (2) Badminton is evolving towards longer rallies with greater rest intervals, resulting in longer matches. (3) The badminton match generated muscle damage, however, the level of muscle damage reached after a badminton match did not produce a decrease in muscle performance. (4) The ingestion of an energy drink containing caffeine might be an effective ergogenic nutritional supplement to increase jump performance and activity patterns during the game in elite badminton players.

With the best of intentions: Is it possible to meet the CARI guidelines?

The CARI1 draft dialysis guidelines propose evidence based targets for biochemical and haematological parameters in ESRF. As part of a prospective randomised trial we investigated our ability to apply the CARI and National Heart Foundation of Australia targets to a representative dialysis population. All patients aged between 18���80 yrs were encouraged to enroll regardless of prior history of non-compliance or co-morbidity. Patients were randomised to either usual care (U;n = 44) or focussed care (F;n = 45). Usual care involved monthly blood tests and pysician review second monthly. In addition focus care patients had a monthly review in a physician supervised trial clinic run by nurses. The groups were comparable at baseline in terms of age, gender, dialysis modality, proportion of diabetics, time on dialysis, haemoglobin, ferritin, % saturation, parathyroid hormone, serum corrected calcium, serum phosphate, total cholesterol and LDL. At 6 months there had been significant improvements in PTH (p < 0.05), total cholesterol (p < 0.05) and LDL (p < 0.001), and a trend to better BP control. The proportion of patients meeting targets at 6 months were as follows: tot chol < 5 mmol/l-U 63%, F 82%; LDL < 3 mmol/l-U 75%, F 91%; phosphate < 1.8 mmol/l- U 42%, F 62%; PTH < 21 pmol/l-U 21%, F 40%; BP sys < 140 mmHg-U 41% F 46%; Hb > 11.5 g/dl U 58% F 64%. In spite of an intensive programme to maximise management of the haematological and biochemical parameters in patients with ESRF it appears that in a significant proportion of patients these targets could not be reached. 1The CARI Guidelines (Caring for Australians with Renal Impairment). Australian Kidney Foundation & Australia New Zealand Society of Nephrology, 2001.

Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT ��� 6-Mercaptopurine (6-MP) and azathioprine (AZA) are both inactive prodrugs that require intracellular activation into the active 6-thioguanine nucleotides (6-TGNs). ��� This metabolic process undergoes three different competitive pathways that are catalysed by three different enzymes; xanthine oxidase (XO), thiopurine methyltransferase (TPMT) and inosine triphosphatase (ITPA), all of which exhibit genetic polymorphisms. ��� Although the impact of genetic variation in the TPMT gene on treatment outcome and toxicity has been demonstrated, the role of other polymorphisms remains less well known. WHAT THIS STUDY ADDS ��� New information on the allelic variation of these three enzymes (XO, TPMT and ITPA) and their influence on 6-MP/AZA metabolism and toxicity. ��� Confirmation of the association of TPMT polymorphism with haematological toxicity. ��� Identified potential genetic characteristics that may contribute to higher risk of adverse events (such as ITPA IVS2+21A���C mutation). AIMS - To examine the allelic variation of three enzymes involved in 6-mercaptopurine/azathioprine (6-MP/AZA) metabolism and evaluate the influence of these polymorphisms on toxicity, haematological parameters and metabolite levels in patients with acute lymphoblastic leukaemia (ALL) or inflammatory bowel disease (IBD). METHODS - Clinical data and blood samples were collected from 19 ALL paediatric patients and 35 IBD patients who were receiving 6-MP/AZA therapy. All patients were screened for seven genetic polymorphisms in three enzymes involved in mercaptopurine metabolism [xanthine oxidase, inosine triphosphatase (C94���A and IVS2+21A���C) and thiopurine methyltransferase]. Erythrocyte and plasma metabolite concentrations were also determined. The associations between the various genotypes and myelotoxicity, haematological parameters and metabolite concentrations were determined. RESULTS - Thiopurine methyltransferase variant alleles were associated with a preferential metabolism away from 6-methylmercaptopurine nucleotides (P = 0.008 in ALL patients, P = 0.038 in IBD patients) favouring 6-thioguanine nucleotides (6-TGNs) (P = 0.021 in ALL patients). Interestingly, carriers of inosine triphosphatase IVS2+21A���C variants among ALL and IBD patients had significantly higher concentrations of the active cytotoxic metabolites, 6-TGNs (P = 0.008 in ALL patients, P = 0.047 in IBD patients). The study confirmed the association of thiopurine methyltransferase heterozygosity with leucopenia and neutropenia in ALL patients and reported a significant association between inosine triphosphatase IVS2+21A���C variants with thrombocytopenia (P = 0.012). CONCLUSIONS - Pharmacogenetic polymorphisms in the 6-MP pathway may help identify patients at risk for associated toxicities and may serve as a guide for dose individualization.

Atividade toxicol��gica do extrato das folhas de Kalanchoe brasiliensis em camundongos Swiss

The species of the genus Kalanchoe (Crassulaceae) are widely used in Brazil as a medicinal product to treat cough, boils, gastritis and other diseases. In this scenario stands out K. brasiliensis, popularly known as coirama or sai��o. This paper aims at the oral exposure of mice to a hydroalcoholic extract of leaves of Kalanchoe brasiliensis. The animals (total of 100) were divided into 12 groups (6 males and 6 females) for the acute assessment; and groups of 10 for subchronic evaluation. Test groups were treated with doses of 250 mg / kg, 500 mg / kg, 1000 mg / kg and 2000 mg / kg and the control group received 0.9% saline. The animals were observed for 14 days for acute evaluation and 30 days for subchronic evaluation, and in that period analyzed the appearance of clinical signs, changes in weight and consumption of water and food. After the observation period, histopathological analysis of the organs, biochemical serum and haematological parameters for the assessment of the subchronic groups were processed. Differences and changes in body weight were not observed among the groups, nor consumption of water and food, there were no deaths among the groups in the two types of assays. Histopathological analysis showed some alterations compatible with low acute hepatic toxicity. The results of blood glucose, triglycerides, ALT, urea and creatinine showed differences between the control group and the test concentrations studied (p <0.05), but these differences do not show relevant change in the clinical picture of animals. The results showed that the extract K. brasiliensis has low acute toxicity at the doses used and no toxicity when administered for 30 days. This highlights the importance of this species as future and promising candidate for phytotherapics, so has its pharmacological trials completed.

Haemophagocytic Syndrome in a 19-Year-Old Male with Plasmodium falciparum Malaria

Objectives: Infectious agents triggering haemophagocytic lymphohistiocytosis (HLH) primarily involve the herpes virus group. We report a case of HLH precipitated by Plasmodium falciparum. Materials and methods: Clinical and laboratory findings in a patient presenting with fever were collected. After confirmation of acute malaria, anti-malarial treatment was administered. Results: Despite initial favourable evolution, the patient developed fever again together with a worsening of the haematological parameters and increased ferritin levels. A bone marrow biopsy confirmed the diagnosis of HLH. Conclusion: This case illustrates that HLH should be considered in the differential diagnosis of acute malaria in patients with persisting fever and pancytopenia.