Exercise-based cardiac rehabilitation increases daily physical activity of patients following myocardial infarction: subanalysis of two randomised controlled trials.

OBJECTIVE: To assess the effects of an exercise-based cardiac rehabilitation programme on daily physical activity levels of patients following myocardial infarction. DESIGN: Subanalysis of two randomised, prospective controlled trials. SETTING: Outpatient clinic of a secondary hospital. PARTICIPANTS: Fifty consecutive patients randomised to the exercise group {n=25; 23 males; mean age 54 [standard deviation (SD) 9] years} or the control group [n=25; 20 males; mean age 58 (SD 9) years]. INTERVENTIONS: The exercise group participated in an 8-week aerobic exercise programme plus usual medical care and follow-up. The control group received usual medical care and follow-up. MAIN OUTCOME MEASURES: The primary outcome measure was change in time spent undertaking moderate-to-vigorous physical activity per day, assessed by accelerometer over 7 consecutive days. Secondary outcome measures were cardiorespiratory fitness, body mass, and resting blood pressure and heart rate. RESULTS: Moderate-to-vigorous physical activity levels increased significantly in the exercise group [43.2 (SD 36.3) to 53.5 (SD 31.9) minutes/day, P=0.030], and remained unchanged in the control group [40.8 (SD 26.2) to 36.8 (SD 26.5) minutes/day, P=0.241] from baseline to the end of the programme. Cardiorespiratory fitness increased significantly in the exercise group (mean difference 2.8; 95% of the difference 1.3 to 4.4ml/kg/minute, P=0.001) after the 8-week programme. CONCLUSIONS: In patients under optimal medication following myocardial infarction, participation in an 8-week exercise-based cardiac rehabilitation programme was found to improve physical activity levels consistent with health-related benefits. Future studies are needed to determine whether the increase in physical activity is maintained in the long term.

Economic analysis of vaccination to control bovine brucellosis in the States of Sao Paulo and Mato Grosso, Brazil.

Brucellosis is a zoonotic disease that causes important economic losses in Brazil, and the country has therefore established a national program for its control and eradication. Using data generated in the last national brucellosis survey, we conducted an economic analysis in two Brazilian States with different brucellosis status, Mato Grosso (with high prevalence) and Sao Paulo (with low prevalence). The economic analysis was based on the calculation of the additional benefits and costs of controlling bovine brucellosis through the vaccination of heifers aged between 3 and 8 months with S19 vaccine, considering maximal and minimal impacts of the disease. The analysis showed that vaccinating 90% of the replacement heifers aged 3-8 months of age offers the best economic performance in a vaccination program against bovine brucellosis if compared to vaccination rates of 70% and 80%. Moreover, regions with higher prevalences of bovine brucellosis would experience significant economic advantages when implementing a vaccination strategy to control the disease. This economic analysis will allow decision makers to plan more economically effective vaccination programs.

GNAS A-1121G variant is associated with improved diastolic dysfunction in response to exercise training in heart failure patients.

ß1-adrenergic receptors (ADRB1) and Gαs proteins (GNAS) play important roles in the regulation of cardiac function. The present study sought to investigate whether ADRB1 Arg389Gly (rs1801253), GNAS -1211 G/A (rs6123837) and GNAS 2291 C/T (rs6026584) variants are associated with left ventricular function and exercise tolerance in heart failure patients. 61 heart failure patients completed a 6-month exercise-training programme. Left ventricular ejection fraction (LVEF), mitral inflow velocities (deceleration time, and E/A ratio) and exercise tolerance (METs) were assessed at baseline and following exercise training. There were no associations between the studied variants and LVEF or E/A ratio measured at baseline and after exercise training. Deceleration time of early mitral flow was higher at baseline in GNAS -1211G allele carriers compared with -1211A allele homozygotes (P<0.05). Exercise training attenuated deceleration time in -1211G allele carriers (P<0.05) but not in -1211A allele homozygotes. Moreover, ADRB1 389Gly homozygotes had a greater training-induced increase in exercise tolerance than 389Arg homozygotes (P=0.04). This study shows that the functional GNAS -1121 G/A polymorphism is associated with diastolic function at baseline and in response to exercise training in heart failure patients. Furthermore, our data suggest that ADRB1 Arg389Gly polymorphism may influence exercise tolerance.

Exercise training increases interleukin-10 after an acute myocardial infarction: a randomised clinical trial.

The present study assessed the effects of exercise training on biomarkers of inflammation in postinfarction patients. This single-centre prospective randomized controlled trial encompassed 42 patients after the first myocardial infarction divided into exercise-training (n=22) or usual care (n=20) groups. Complete randomization was performed by choosing one of 2 sealed envelopes. The exercise-training group participated in an 8-week programme comprising 3 aerobic exercise sessions per week. The control group received usual care. The main measures were changes in circulating levels of C-reactive protein, interleukin (IL)-6 and -10, soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1), anthropometrics, dietary intake, daily physical activity, and cardiorespiratory fitness. 4 patients terminated the study prematurely, leaving 38 for the statistical analysis (exercise-training, n=20; control group, n=18). In comparison to control group, exercise-training group improved IL-10 levels [1.7(7.0) vs. - 0.3(2.4) pg/mL, P<0.05], daily moderate-intensity physical activity (12.9±21.3 vs. - 0.7±13.4 min, P<0.05), and cardiorespiratory fitness (3.0±3.5 vs. 0.3±4.1 ml/min/kg, P<0.05). Additionally, the change in VCAM-1 and ICAM-1 levels was significantly higher in the control group (respectively, 26.6±112.1 vs. 94.1±90.0 ng/mL and 7.3±41.0 vs. 35.0±39 ng/mL, P<0.05). In conclusion, exercise training improved the inflammatory profile in post myocardial infarction patients by enhancing the anti-inflammatory cytokine IL-10.

Is there an interaction between BDKRB2 -9/+9 and GNB3 C825T polymorphisms and elite athletic performance?

The -9 deletion allele in the BDKRB2 -9/+9 polymorphism was associated previously with improved endurance performance. We compared the frequency distribution of the BDKRB2 -9/+9 (rs5810761) polymorphism between athletes (n=155) of sports with different demands (endurance runners; n=74 vs sprinters; n=81) as well as between athletes of different competitive levels (elite level; n=46 vs national level; n=109). These results were compared with those of 240 non-athletic healthy individuals. We also tested the influence of the interaction between the BDKRB2 -9/+9 and the GNB3 C825T (rs5443) genotypes in relation to endurance performance. Genotype distribution and allele frequencies were found to be similar in the endurance athlete, sprinter, and control groups (P=0.83 for genotype distribution and P=0.9 for allele frequencies). Similarly, no statistical differences were found between the subgroups of elite-level endurance athletes and national-level endurance athletes, or between elite-level and national-level sprinters (P>0.09 for all comparisons). There was no interaction between BDKRB2 -9/+9 and GNB3 C825T polymorphisms in relation to endurance performance (P=0.16 for interaction effect). In conclusion, the BDKRB2 +9/-9 polymorphism is not associated with endurance performance, at least among Israeli athletes, and the GNB3TT+BDKRB2 -9/-9 "optimal genotype" is not associated with endurance performance.

CK-MM gene polymorphism does not influence the blood CK activity levels after exhaustive eccentric exercise.

Gene variants, such as creatine kinase (CK) polymorphisms, have been suggested to explain the inter-individual blood CK response to eccentric exercise. However, since this association is still doubtful, the purpose of this study was to analyse the relationship between the magnitudes of the CK response to exercise with the occurrence of muscle CK-MM NcoI polymorphism in young healthy subjects. Blood CK activity was assessed in 70 subjects immediately before and 3, 24, 48, 72, 96, 120, 168 h after strenuous eccentric exercise. Based on the amount of CK release by each subject, the sample was distributed in quartiles and the genotype and allele frequency distribution was compared among quartiles. Despite the inter-individual variability of CK response observed between subjects, there were no differences in genotype and allele frequencies among quartiles. The results allowed us to conclude that CK response after exhaustive eccentric exercise is not associated with CK-MM Ncol polymorphism.

Is there an ACE ID - ACTN3 R577X polymorphisms interaction that influences sprint performance?

Functional R577X (rs.1815739) and ID (rs.5186) polymorphisms in the alpha-actinin-3 ( ACTN3) and the angiotensin converting enzyme (ACE) genes, respectively, have been associated with sprint performance. The aim of this study was to determine their effect on sprint performance among 81 Israeli sprinters and 240 healthy controls. Results revealed that the ACE II genotype+ ACTN3 R allele (P=0.003 for sprinters vs. controls), and the ACTN3 RR genotype +ACE I allele (P=0.001 for sprinters vs. controls) might be the genotype for sprinters. In the whole cohort the probability of ACTN3 RR genotype+ ACE I allele being a sprinter (odds ratio 2.67, 95% confidence interval 1.45-4.93) and of ACE II genotype+ ACTN3 R allele being a sprinter (odds ratio 3.57, 95% confidence interval 1.78-7.15) was significantly higher than that in the controls. In conclusion, the above data suggest that ACE ID/ ACTN3 R577X genotype combination is associated with sprint ability. However, ACE ID/ ACTN3 R577X genotype combination is not related to the level of performance.

Situação epidemiológica da brucelose bovina no Estado da Bahia / Epidemiological situation of bovine brucellosis in the State of Bahia, Brazil

O trabalho consistiu em estratificar o Estado da Bahia em quatro regiões com características homogêneas (circuitos produtores) para que fossem amostradas aleatoriamente, em cada uma delas, 300 propriedades. Em cada propriedade foram escolhidas, de forma aleatória, 10 a 15 fêmeas bovinas adultas, das quais foi obtida uma amostra de sangue. No total, foram amostrados 10.816 animais, provenientes de 1.413 propriedades. O protocolo de testes utilizado foi o da triagem com o teste do antígeno acidificado tamponado (Rosa Bengala) e a confirmação dos positivos com o teste do 2-mercaptoetanol. O rebanho foi considerado positivo se pelo menos um animal reagiu às duas provas sorológicas. As prevalências de focos e a de fêmeas adultas soropositivas do Estado foram de 4,2 por cento [3,1-5,3 por cento] e 0,66 por cento [0,41-0,93 por cento], respectivamente. Para os circuitos produtores foram: circuito 1, 5,8 por cento [3,6-8,7 por cento] e 0,86 por cento [0,41-1,3 por cento]; circuito 2, 3,1 por cento [1,5-5,6 por cento] e 1,2 por cento [0,25-2,1 por cento]; circuito 3, 6,3 por cento [4,0-9,3 por cento] e 1,7 por cento [0,66-2,7 por cento]; e circuito 4, 0,60 por cento [0,07-2,2 por cento] e 0,07 [0,00-0,21 por cento]. Para a análise de fatores de riscos associados à doença foi aplicado um questionário epidemiológico em cada propriedade visitada. Os fatores de risco (odds ratio, OR) associados à condição de foco foram: compra de reprodutores (OR= 2,27) e presença de áreas alagadiças (OR= 1,76). A vacinação de fêmeas de três até oito meses de idade foi um fator de proteção (OR= 0,53).

A study to characterize the epidemiological situation of bovine brucellosis in the State of Bahia was carried out in 2004. The State was divided into four similar production regions, 300 herds were randomly sampled in each region, and 10 to 15 adult bovine females were sampled in each of these herds. A total of 10,816 serum samples from 1,413 herds were collected. The serum samples were screened for antibodies to Brucella spp. by the Rose-Bengal Test (RBT), and all RBT-positive sera were re-tested by the 2-mercaptoethanol test (2-ME) for confirmation. A herd was considered positive if at least one animal was positive on both RBT and 2-ME tests. The prevalence of infected herds and seropositive adult bovine females in Bahia State were: 4.2 percent [3.1-5.3 percent] and 0.66 percent [0.41-0.93 percent], respectively. In the production regions, prevalence of infected herds and animals were, respectively: region 1, 5.8 percent [3.6-8.7 percent] and 0.86 percent [0.41-1.3 percent]; region 2, 3.1 percent [1.5-5.6 percent] and 1.2 percent [0.25-2.1 percent]; region 3, 6.3 percent [4.0-9.3 percent] and 1.7 percent [0.66-2.7 percent]; and region 4, 0.60 percent [0.07-2.2 percent] and 0.07 percent[0.00-0.2 percent]. In each herd, an epidemiological questionnaire was applied. The risk factors (odds ratio, OR) associated with the presence of the infection were: purchase of breeding animals (OR = 2.27) and presence of flood areas (OR= 1.76). Vaccination of heifers from three to eight months of age was a protective factor (OR=0.53).

In vitro and in vivo properties of usnic acid encapsulated into PLGA-microspheres.

Microparticles will probably play a promising role in the future of chemotherapy. These polymeric delivery systems are capable of maximizing the therapeutic activity while reducing side effects of anti-cancer agents. Usnic acid (UA) is a secondary metabolite produced by lichens, which exhibits an anti-tumour activity. In this study, PLGA-microspheres containing usnic acid from Cladonia substellata were prepared by the double emulsion method, with or without PEG as stabilizer. The morphology of the microspheres was examined by optical and scanning electron microscopy. The in vitro kinetic profile of usnic acid loaded-microspheres was carried out by dissolution testing. The usnic acid content was analysed by HPLC. The cytotoxicity of free and encapsulated usnic acid was evaluated against HEp-2 cells using the MTT method. The anti-tumour assay was performed in mice against Sarcoma-180 tumour (UA 15 mg kg(-1) weight body/day) during 7 days. Animals were then sacrificed and tumour and organs were excised for histopathological analysis. Microspheres presented a smooth spherical surface with a mean diameter of 7.02 +/- 2.72 microm. The usnic acid encapsulation efficiency was approximately 100% (UA 10 mg 460 mg(-1) microspheres). A maximum release of 92% was achieved at the fifth day. The IC50 values for free and encapsulated usnic acid were 12 and 14 microg ml(-1), respectively. The encapsulation of usnic acid into microspheres promoted an increase of 21% in the tumour inhibition as compared with the free usnic acid treatment. In summary, usnic acid was efficiently encapsulated into PLGA-microspheres and the microencapsulation improved its anti-tumour activity.

Bioequivalence of two lamivudine tablet formulations.

The present study describes the determination of the bioavailability of a new commercial tablet formulation of lamivudine (CAS 134678-17-4) compared with a reference formulation. The comparative bioequivalence of the test and a reference formulation (each 3 x 150 mg) was assessed in 24 healthy volunteers by means of a randomized two-way crossover design. Prior to the study both the test and reference formulations were examined for conformation to chromatographic purity and drug content. Each volunteer received the test (T) and the reference formulation (R) with a one-week drug-free interval between administrations. The plasma concentrations of T were monitored over a period of 12 h after drug administration using a sensitive HPLC method. Pharmacokinetic parameters for T were determined from plasma concentration-time data. Statistical tests were carried out at 90% confidence intervals using a parametric method (three-way ANOVA) for AUC and Cmax, and non-parametric method for Tmax. The present study showed that both formulations were bioequivalent for the geometric mean of AUC(0-12), AUC0-infinity), Cmax, and Tmax at the 90% confidence interval. The bioavailability of the test (%) was 96.7, 93.3, 99.7, 100.3, respectively. The T:R ratio was, in each case, well within the acceptable range of 100 +/- 20%.

A New Dietary Supplement Based on Bovine Blood: Recovering Brazilian Children from Malnutrition.

Two compounds ("Prothemol" and "Plasmel"), based on bovine blood as source of high quality-protein, were tested as supplement for malnourished children. Prothemol is a powder containing desiccated bovine red cells, with 23.32 g% protein and 18.8 mg% iron, without any limiting amino acid. Plasmel (a syrup) contains 44.7% bovine plasma, 54.3% saccharose and 1500 IU% retinol. Children, 32-60 month old, from a day-nursery service in Recife, Brazil, received Prothemol + Plasmel for 90 (n = 14) or 180 days (n = 8). When compared to age-matched control children (n = 12 and n = 6, respectively), they presented significantly higher increments in weight and height, and in some haematological parameters. Clinical signs associated to malnutrition (faces suggesting suffering or sadness; brightnessless eyes; apathy; reduced mobility; reduced communication with their classmates and adults) were found in 12 treated children (85.7%) and in 9 controls (75%). Recovery from these signs begun after 51 ± 20.6 and 103.5 ± 14.6 days, for the treated and control groups, respectively (P < 0.05) and occurred in 100% of the treated children and in 67% (6 of 9 children) in the controls. We suggest that Prothemol + Plasmel is an effective dietary supplement to help treating malnutrition in children, recovering them from clinical signs indicative of improving neural functions.

Synthesis and cytotoxic activity of N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal.

Five new N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal were synthesized. Safrole, a natural product obtained from sassafras oil (Ocotea pretiosa), was oxidized to alcohol using BH3-THF and H2O2, followed by oxidation to aldehyde using pyridinium dichromate (PDC) and condensation with five N-substituted derivatives of thiosemicarbazide. Tests were performed to evaluate the cytotoxic activity with continuous chain KB cells (epidermoide carcinoma of the floor of the mouth). Compounds 5 and 6 showed IC50 values of 1.5 and 4.6 micrograms/ml, respectively.

Synthesis of some 4-oxo-delta 2-thiazolin-2-ylhydrazones as potential antiprotozoal agents.

Several 4-oxo-delta 2-thiazolin-2-ylhydrazone derivatives 6 (6-1 - 6-19) derived from the cyclization reaction between the thiosemicarbazones 5 and homologous alpha-chloroacids were prepared. Only compound 6-2 was found to be active against Entamoeba histolytica and Trichomonas vaginalis.

Asymmetric synthesis and biological evaluation of beta-L-(2R,5S)- and alpha-L-(2R,5R)-1,3-oxathiolane-pyrimidine and -purine nucleosides as potential anti-HIV agents.

In order to study the structure-activity relationships of L-oxathiolanyl nucleosides as potential anti-HIV agents, a series of enantiomerically pure L-oxathiolanyl pyrimidine and purine nucleosides were synthesized and evaluated for anti-HIV-1 activity in human peripheral blood mononuclear (PBM) cells. The key intermediate 8 was synthesized starting from L-gulose via 1,6-thioanhydro-L-gulopyranose. The acetate 8 was condensed with thymine, 5-substituted uracils and cytosines, 6-chloropurine, and 6-chloro-2-fluoropurine to give pyrimidine and purine nucleosides. Upon evaluation of these final nucleosides, the 5-fluorocytosine derivative 51 was found to be the most potent compound among those tested. In the case of 5-substituted cytosine analogues, the antiviral potency was found to be in the following decreasing order: cytosine (beta-isomer) > 5-iodocytosine (beta-isomer) > 5-fluorocytosine (alpha-isomer) > 5-methylcytosine (alpha-isomer) > 5-methylcytosine (beta-isomer) > 5-bromocytosine (beta-isomer) > 5-chlorocytosine (beta-isomer). Among the thymine, uracil, and 5-substituted uracil derivatives, thymine (alpha-isomer) and uracil (beta-isomer) derivatives exhibited moderate anti-HIV activity. In the purine series, the antiviral potency is found to be in the following decreasing order: adenine (beta-isomer) > 6-chloropurine (beta-isomer) > 6-chloropurine (alpha-isomer) > 2-NH2-6-Cl-purine (beta-isomer) > guanine (beta-isomer) > N6-methyladenine (alpha-isomer) > N6-methyladenine (beta-isomer). The cytotoxicity was also determined in human PBM cells as well as Vero cells. None of the synthesized nucleosides was toxic up to 100 microM in PBM cells.

1,3-dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes.

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV-1 agents, various enantiomers of pure dioxolanylpurine nucleosides were synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 1, which was synthesized in nine steps from 1,6-anhydro-beta-D-mannose, was condensed with 6-chloropurine, 6-chloro-2-fluoropurine, and 2,6-dichloropurine in the presence of TMS triflate. The chloro or fluoro substituents were readily converted into amino, N-methylamino, hydroxy, methoxy, thiol, and methylthio under appropriate reaction conditions. Upon evaluation of these dioxolanes, the guanine derivative 24 exhibited the most potent anti-HIV-1 activity without cytotoxicity up to 100 microM in various cells. The decreasing antiviral activity order of beta-isomers was as follows: guanine > 6-chloro-2-aminopurine > 2-fluoroadenine > or = adenine > or = 2,6-diaminopurine > hypoxanthine > 2-chloroadenine > 6-chloropurine approximately equal to N6-methyladenine approximately equal to 6-mercaptopurine approximately equal to 6-(methylthio)purine.

Asymmetric synthesis of 1,3-dioxolane-pyrimidine nucleosides and their anti-HIV activity.

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides. Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic. The order of anti-HIV potency was as follows: cytosine (beta-isomer) greater than thymine greater than cytosine (alpha-isomer) greater than 5-chlorouracil greater than 5-bromouracil greater than 5-fluorouracil derivatives. Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive. Interestingly, alpha-isomer 20 showed good anti-HIV activity without cytotoxicity. As expected, other alpha-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.