Induced acute hyperglycemia modifies the barrier function of the intestinal epithelium by tissue inflammation and tight junction disruption resulting in hydroelectrolytic secretion in an animal model.

Diabetic-metabolic syndrome (MetS-D) has a high prevalence worldwide, in which an association with the rupture of the intestinal epithelium barrier function (IEBF) has been pointed out, but the functional and morphological properties are still not well understood. This study aimed to evaluate the impact of acute hyperglycemia diabetes on intestinal tight junction proteins, metabolic failure, intestinal ion and water transports, and IEBF parameters. Diabetes was induced in male Rattus norvegicus (200-310 g) with 0.5 mL of streptozotocin (70 mg/kg). Glycemic and clinical parameters were evaluated every 7 days, and intestinal parameters were evaluated on the 14th day. The MetS-D animals showed a clinical pattern of hyperglycemia, with increases in the area of villi and crypts, lactulose:mannitol ratio, myeloperoxidase (MPO) activity, and intestinal tissue concentrations of malondialdehyde (MDA), but showed a reduction in reduced glutathione (GSH) when these parameters were compared to the control. The MetS-D group had increased secretion of Na+, K+, Cl-, and water compared to the control group in ileal tissue. Furthermore, we observed a reduction in mRNA transcript of claudin-2, claudin-15, and NHE3 and increases of SGLT-1 and ZO-1 in the MetS-D group. These results showed that MetS-D triggered intestinal tissue inflammation, oxidative stress, complex alterations in gene regulatory protein transcriptions of intestinal transporters and tight junctions, damaging the IEBF and causing hydroelectrolyte secretion.

Analysis of fungal microbiota of ambient air in an intensive care unit in Rio Branco, Acre, Western Amazon, Brazil.

Fungi exhibit three adverse effects on human health: inflammatory, allergic and toxic effects, these implications affect mainly immunodepressed patients. The objective of this work was to analyze the fungal microbiota of the ambient air of an Intensive Care Unit. Three collections were carried out in an Intensive Care Unit in the city of Rio Branco, Acre, Western Amazon, Brazil from March to May 2017. 126 Petri dishes were exposed with the culture medium Agar Sabouraud with chloramphenicol and Agar Mycosel, considering the distribution of the 21 air conditioners, split residential model. The plates were incubated for seven days at room temperature and the growth of Colony Forming Units was observed. Colony counting and isolation for the morphological characterization of the granted fungi was performed. After quantification, the concentration of fungi per cubic meters of air (CFU.m-3) was settled. The third collection had a larger number of colony forming units with 48.6%. In the total of the analyzed samples, filamentous fungi (85.5%) and yeasts (14.5%) were isolated. Thirteen genera of fungi were identified, with the most frequent filaments being Cladosporium spp. 33.0%, Aspergillus spp. 30.4% and Penicillium spp. 19.6%, and yeasts Candida spp. 52.6%, Trichosporon spp. 36.9%. The colony-forming unit per cubic meter (CFU.m-3) did not shown any difference between the Cores in the same collection period, however in the 1st and 3rd collection, Core 1 had the highest average. The fungal microbiota of this Unit presented thirteen different genera potentially pathogenic, revealing the need for monitoring microorganisms and prevention actions.

Dietary patterns and body adiposity in children in Brazil: a cross-sectional study.

OBJECTIVES: Many factors are associated with the increase in total and central body adiposity in children, especially eating habits. This has led to an increasing number of studies analysing food patterns, which consider the synergistic effect of food and nutrient intake on the nutritional status. The objective of this study was to identify the dietary patterns of children aged 4-7 years and associate these with different indicators of total and central body adiposity. STUDY DESIGN: Cross-sectional study METHODS: The study consisted of 403 children from a retrospective cohort in Minas Geraes, Brazil. Four indicators of body adiposity were evaluated: body mass index (BMI), waist-to-height ratio (WHtR) and percentages of total and central body fat (assessed by dual-energy X-ray absorptiometry). The dietary habits of the children were evaluated by identifying the dietary patterns using principal component analysis. The adjustment predictor variables were related to the socio-economic characteristics, lifestyle and duration of exclusive breastfeeding. Food patterns were identified by factor analysis. Linear regression was used to estimate the regression coefficient and the confidence interval, considering statistical significance of α = 5%. RESULTS: Five dietary patterns were identified, which explained 42.3% of the data variance: 'Traditional', 'Unhealthy', 'Milk and chocolate', 'Snack' and 'Healthy'. The multiple linear regression model showed that a greater adherence to the 'Traditional' and 'Unhealthy' patterns was related to higher BMI, WHtR, and total and central body adiposity. CONCLUSION: Children with a higher intake of food from the 'Traditional' and 'Unhealthy' patterns showed an increase in total and central body adiposity.

Intestinal cell migration damage induced by enteropathogenic Escherichia coli strains.

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.

Intestinal cell migration damage induced by enteropathogenic Escherichia coli strains

Epithelial cell migration is an essential response to enteric pathogens such as enteropathogenic Escherichia coli (EPEC). This study aimed to investigate the effects of EPEC infection on intestinal epithelial cell migration in vitro, as well as the involvement of type III secretion system (T3SS) and Rho GTPases. Crypt intestinal epithelial cells (IEC-6) were infected with EPEC strains (E2348/69, ΔescF, and the LDI001 strain isolated from a malnourished Brazilian child) and commensal E. coli HS. Wound migration and cell death assays were performed at different time-points. Transcription and expression of Rho GTPases were evaluated using real-time PCR and western blotting. Overall, EPEC E2348/69 reduced migration and increased apoptosis and necrosis levels compared to EPEC LDI001 and E. coli HS strains. Moreover, EPEC LDI001 impaired cell migration at a higher level than E. coli HS and increased necrosis after 24 hours compared to the control group. The different profiles of virulence genes between the two wild-type EPEC strains, characterized by the absence of espL and nleE genes in the LDI001, might explain the phenotypic results, playing significant roles on cell migration impairment and cell death-related events. Moreover, the type III secretion system is determinant for the inhibition of intestinal epithelial cell migration by EPEC 2348/69, as its deletion prevented the effect. Active Rac1 concentrations were increased in E2348/69 and LDI001-infected cells, while the T3SS-deficient strain did not demonstrate this activation. This study contributes with valuable insight to characterize the mechanisms involved in the impairment of intestinal cell migration induced by EPEC.

Impact of acute undernutrition on growth, ileal morphology and nutrient transport in a murine model.

Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.

Protective role of free and quercetin-loaded nanoemulsion against damage induced by intracerebral haemorrhage in rats.

Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg(-1). Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.

Impact of acute undernutrition on growth, ileal morphology and nutrient transport in a murine model

Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.

The interrelation between aPKC and glucose uptake in the skeletal muscle during contraction and insulin stimulation.

Contraction and insulin increase glucose uptake in skeletal muscle. While the insulin pathway, better characterized, requires activation of phosphoinositide 3-kinase (PI3K) and atypical protein kinase (aPKC), muscle contraction seems to share insulin-activated components to increase glucose uptake. This study aimed to investigate the interrelation between the pathway involved in glucose uptake evoked by insulin and muscle contraction. Isolated muscle of rats was treated with solvent (control), insulin, wortmannin (PI3K inhibitor) and the combination of insulin plus wortmannin. After treatment, muscles were electrically stimulated (contracted) or remained at rest. Glucose transporter 4 (GLUT4) localization, glucose uptake and phospho-aPKC (aPKC activated form) were assessed. Muscle contraction and insulin increased glucose uptake in all conditions when compared with controls not stimulating an effect that was accompanied by an increase in GLUT4 and of phospho-aPKC at the muscle membrane. Contracted muscles treated with insulin did not show additive effects on glucose uptake or aPKC activity compared with the response when these stimuli were applied alone. Inhibition of PI3K blocked insulin effect on glucose uptake and aPKC but not in the contractile response. Thus, muscle contraction seems to stimulate aPKC and glucose uptake independently of PI3K. Therefore, aPKC may be a convergence point and a rate limit step in the pathway by which, insulin and contraction, increase glucose uptake in skeletal muscle.

The effect of age on glucose uptake and GLUT1 and GLUT4 expression in rat skeletal muscle.

During the life span, phenotypic and structural modifications on skeletal muscle contribute to a reduction on glucose uptake either in basal state or triggered by insulin, but the underlying mechanisms for this decline are not entirely identified. A reduction in the expression of skeletal muscle glucose transporters (GLUTs), glucose transporter type 1 (GLUT1) and glucose transporter type 4 (GLUT4), has been associated to such phenomena, but unlike the case of insulin, only few studies have addressed the effect of age on muscle-contraction-induced glucose uptake. The aim of the study was to investigate the influence of age on GLUT1 and GLUT4 expression in skeletal muscle and its relation to the glucose uptake induced by muscle contraction. For this purpose, soleus muscle from Wistar rats aged 4, 10, 22 and 42 weeks were isolated and electrically stimulated (30 min, 10 Hz, 20 V, 0.2 ms). After stimulation, glucose uptake and GLUT1 and GLUT4 expression and localisation were evaluated. Muscle contraction caused an increase in glucose uptake in all studied groups. In addition, the absolute rates of glucose uptake were negatively correlated with age. The expression of GLUT4 was lower in older animals, whereas no relation between age and GLUT1 expression was found. Immunohistochemistry confirmed the ontogenic effect on GLUT4 expression and suggested an age-related modification on GLUT1 distribution within the muscle fibres; for instance, this protein seems to be present mainly out of the sarcoplasm. The present findings demonstrate that the ability of muscle contraction to increase glucose uptake is not influenced by age, whereas glucose uptake under basal conditions decreases with age.

Prevalence of newcastle disease virus in broiler chickens (gallus gallus) in Brazil

This study was carried out during 2002/2003, aiming to determine the prevalence of virulent Newcastle disease virus strains (NDV) in Brazilian commercial poultry farms. Clinical samples were obtained from the Southeastern, Southern and Central-Western regions, which comprise the main area of the Brazilian poultry production. Serum samples and tracheal and cloacal swabs of 23,745 broiler chickens from 1,583 flocks, including both vaccinated chickens and those with no vaccination information, were tested for NDV using a diagnostic ELISA kit. The seropositivity was 39.1 percent, and the isolation percentage by flock varied from 1.0 to 7.6 percent, and by region from 6.5 to 58.4 percent. Higher isolation rates (74.3-83.3 percent) were obtained after three passages in embryonated chicken eggs. All isolates preliminarily identified as NDV were characterized as nonpathogenic strains, as their Intracerebral Pathogenicity Index (ICPI) was below 0.7. Based on results of this study, Brazil can claim a virulent NDV-free status for commercial flocks.

A survey for maintenance of virulent newcastle disease virus-free area in poultry production in Brazil

In 2003, Brazil was recognized as a pathogenic Newcastle Disease Virus (NDV) strain-free country for commercial poultry. This research was conducted in Brazil between December 2003 and March 2005 to verify the maintenance of this virulent NDV-free status. Serum samples from 5,455 flocks for commercial poultry farms were collected, comprising 81,825 broiler chickens. The farms were located in nine states of the country, grouped in three geographic regions. Serological evidence of NDV infection was detected in 28.8 percent of the surveyed farms. However, all fifteen viruses isolated and identified as Newcastle Disease Virus (NDV) were characterized as nonpathogenic strains, based on the Intracerebral Pathogenicity Index. These results showed that Brazil preserves the virulent NDV-free status for commercial flocks.

Prevalence of newcastle disease virus in broiler chickens (Gallus gallus) in Brazil.

This study was carried out during 2002/2003, aiming to determine the prevalence of virulent Newcastle disease virus strains (NDV) in Brazilian commercial poultry farms. Clinical samples were obtained from the Southeastern, Southern and Central-Western regions, which comprise the main area of the Brazilian poultry production. Serum samples and tracheal and cloacal swabs of 23,745 broiler chickens from 1,583 flocks, including both vaccinated chickens and those with no vaccination information, were tested for NDV using a diagnostic ELISA kit. The seropositivity was 39.1%, and the isolation percentage by flock varied from 1.0 to 7.6%, and by region from 6.5 to 58.4%. Higher isolation rates (74.3-83.3%) were obtained after three passages in embryonated chicken eggs. All isolates preliminarily identified as NDV were characterized as nonpathogenic strains, as their Intracerebral Pathogenicity Index (ICPI) was below 0.7. Based on results of this study, Brazil can claim a virulent NDV-free status for commercial flocks.

A survey for maintenance of virulent newcastle disease virus-free area in poultry production in Brazil.

In 2003, Brazil was recognized as a pathogenic Newcastle Disease Virus (NDV) strain-free country for commercial poultry. This research was conducted in Brazil between December 2003 and March 2005 to verify the maintenance of this virulent NDV-free status. Serum samples from 5,455 flocks for commercial poultry farms were collected, comprising 81,825 broiler chickens. The farms were located in nine states of the country, grouped in three geographic regions. Serological evidence of NDV infection was detected in 28.8% of the surveyed farms. However, all fifteen viruses isolated and identified as Newcastle Disease Virus (NDV) were characterized as nonpathogenic strains, based on the Intracerebral Pathogenicity Index. These results showed that Brazil preserves the virulent NDV-free status for commercial flocks.

Centromeres: old tales and new tools.

The centromere is a specialised region of the eukaryotic chromosome that directs the equal segregation of sister chromatids into two daughter cells during mitosis. In mitosis, the kinetochores mediate (1) microtubule capture and chromosome alignment at a metaphase plate; (2) the correction of improper microtubule attachments; (3) the maintenance of an active checkpoint until bi-orientation is achieved by the whole complement of chromosomes; (4) the establishment of tension within the centromere which, in turn, contributes to silencing of the spindle checkpoint and triggers the onset of anaphase. In this review, we will analyse how centromeres are organised with respect to chromatin types and arrangements.

[Attitude toward smoking among smoking and non-smoking officials of the Federal University of Sao Paulo, Brazil: comparative analysis of smokers and non-smokers]. / Actitud ante el tabaquismo de funcionarios fumadores y no fumadores de la Universidad Federal de São Paulo, Brasil: análisis comparativo de fumadores y no fumadores.

OBJECTIVE: To study the attitudes toward smoking of employees of the Federal University of Sao Paulo as a step toward implanting a consensualized anti-smoking program for the institution. METHOD: We designed and distributed anonymous, self-completed questionnaires with 51 multiple-choice questions, which were returned by 2,613 (48.6%) employees, professors, medical residents, nurses and students. RESULTS: Four hundred thirty-eight (16.8% of the population) of the respondents were smokers and 456 (17.5%) were non-smokers. For 84% smoking started between the ages of 11 and 20 years. Most smokers were between 31 and 40 years of age, and the prevalence of ex-smokers was highest in respondents over the age of 60. Seventy-eight percent of the smokers smoked at work. Both smokers and non-smokers reported some type of discomfort caused by cigarette smoke, mainly smell in clothes and hair (62.7% of smokers versus 59% of non-smokers, NS). The proportion who opted for a totally smoke-free environment was 37.5% among non-smokers and 10% among smokers (p < 0.05). Restrictions on smoking in specific places, on the other hand, met with the approval of 82.8% of smokers and 59% of non-smokers (p < 0.05). CONCLUSIONS: We believe that surveys such as this one should be carried out at all institutions, particularly in health care centers, in order to assure that smoking restriction policies are successful and receive the support of most employees, whether they smoke or not. Our data suggest the advisability of creating restricted-smoking zones in the early phase of an institutional anti-smoking campaign designed to lead to a totally smoke-free workplace environment.

[Smoking prevalence at the Federal University of São Paulo, 1996--preliminary data of an institutional program]. / Prevalência de tabagismo na Universidade Federal de São Paulo, 1996--dados preliminares de um programa institucional.

PURPOSE: To evaluate the prevalence of tobacco smoking among health workers, professores, nurses and students of Federal University of São Paulo and the acceptance of an institutional program for quitting smoking. METHODS: We analized the answers of a questionnairy with 51 questions, distributed to people from different categories. RESULTS: The total percentage of answered questionnaires was 48.6% (2613). The answers obtained from health workers were 37.3%, professors 49.0%, nurses 52.7% and students 76.5% The total percentage of smokers at UNIFESP was 15.5%:23.7% for health workers, 18% for professors, 16% for nurses and 8.6% for students. There was no significant statistical difference between the prevalence of smoking among females (17.3%) and males (16.3%). The age of major prevalence of smoking was between 31 to 40 years (26.6%). For all ages, people who have university level smoked less, independent of sex. Eighty three percent (83%) of the UNIFESP workers and students are worried of being passive smokers. Between the smokers, 55% were thinking of quiting and 42% declared that need some help to quit. CONCLUSION: We concluded that educational programs and help for cessation at institutional level are necessary and well accepted at UNIFESP, and the completion of these programs will contribute to the obeying of the prohibitive laws of no smoking within the community.

Prevalência de tabagismo na Universidade Federal de Säo Paulo, 1996: dados preliminares de um programa institucional / Smoking prevalence at Universidade Federal de Säo Paulo, 1996: preliminary data of an institutional program

Objetivo. O conhecimento da prevalência do tabagismo é necessário para a realizaçao de programas institucionais adequados que visem a diminuiçao do número de fumantes. O objetivo do trabalho foi verificar a prevalência do tabagismo entre funcionários, docentes, enfermeiros e alunos da Universidade Federal de Sao Paulo e a aceitabilidade de um programa antifumo. Pacientes e Métodos. Foram analisadas as respostas obtidas a partir de um questionário contendo 51 questoes, distribuídos para as diferentes categorias. Resultados. A porcentagem total de questionários respondidos foi de 48,6 por cento (2.613) sendo 37,3 por cento para funcionários, 49,0 por cento para docentes, 52,7 por cento para enfermeiras e 76,5 por cento para alunos. Verificou-se que a porcentagem total de fumantes na UNIFESP foi de 15,5 por cento, sendo 23,7 por cento entre funcionários, 18 por cento entre docentes, 16 por cento entre enfermeiros e 8,6 por cento entre alunos. A faixa etária de maior prevalência de fumantes foi a de 31 a 40 anos (26,6 por cento). Nao houve diferença estatística entre a prevalência de fumantes entre homens e mulheres. Em ambos os sexos, para todas as faixas etárias, os indivíduos com maior nível de instruçao fumavam menos. Das pessoas que responderam o questionário, 82,5 por cento estavam preocupadas em serem fumantes passivas. Dos fumantes, 55 por cento estao pensando em largar de fumar e 42 por cento julgam precisar de algum tipo de ajuda. Conclusao. Programas educacionais e de cessaçao do tabagismo em nível institucional sao necessários e bem aceitos na UNIFESP, devendo ser realizados para que as leis de restriçao do fumo dentro da instituiçao sejam efetivamente cumpridas.

Effects of almitrine on the ventilatory control, breathing pattern and maximal exercise tolerance in hypoxemic patients with chronic obstructive pulmonary disease.

Almitrine bismesylate improves arterial blood gases in patients with chronic obstructive pulmonary disease (COPD), but side effects such as increase of ventilatory drive and dyspnea have been reported in some studies. We studied 18 COPD patients (mean age = 59.1 years; mean FEV1 = 0.92 1; mean PaO2 = 58.6 mmHg) in a double-blind randomized study using placebo or almitrine 50 mg twice a day by mouth, for 60 days. In contrast to the placebo group, 40% of the patients in the almitrine group presented a significant increase in PaO2 and a decrease in P(A-a)O2 > or = 5 mmHg during submaximal exercise after 60 days of treatment. Ventilatory drive and the breathing pattern were measured at rest and during submaximal exercise. Both groups showed high levels of ventilatory drive and a tachypneic breathing pattern before drug treatment and no modification was found 30 and 60 days after treatment. Metabolic, cardiovascular and ventilatory variables were studied during an incremental to maximum exercise symptom-limited test (cycloergometry). Maximal VO2 ranged from 46 to 52% and heart rate from 76 to 78% in relation to the predicted values. The percent ratio of ventilation at maximal exercise to maximal voluntary ventilation at rest ranged from 86 to 94%. These results show that the reduction of ventilatory capacity was the main factor decreasing the aerobic performance of our COPD patients. Maximal exercise tolerance (VO2 max) did not change after almitrine treatment. Negative factors like an increase in neuromuscular drive did not occur, and positive factors like an increase in PaO2 and oxygen transport had no critical influence on exercise performance in our ventilatory-limited COPD patients.

Effects of almitrine on the ventilatory control, breathing pattern and maximal exercise tolerance in hypoxemic patients with chronic obstructive pulmonary disease

Almitrine bismesylate improves arterial blood gases in patients with chronic obstructive pulmonary disease (COPD), but side effects such as increase of ventilatory drive and dyspnea have been reported in some studies. We studied 18 COPD patients (mean age=59.1 years; mean FEV1=0.921; mean PaO2=58.6mmHg) in a double-blind randomized study using placebo or almitrine 50 mh twice a day by mouth, for 60 days. In contrast to the placebo group, 40 per cent of the patients in the almitrine group presented a significant increase in PaO2 and a decrease in P(A-a))2>=5mmHg during submaximal exercise after 60 days of treatment. Ventilatory drive and the breathing pattern were measured at rest and during submaximal exercise. Both goups showed high levels of ventilatory drive and atachypneic breathing pattern before drug tratment and no modification was found 30 and 60 days after treatment. Metabolis, cardiovascular and ventilatory variables were studied during an incremental to maximum exercise symptom-limited test (cycloergometry). Maximal VO2 ranged from 46 to 52 per cent and heart rate from 76 to 78 per cent in relation to the predicted values. The percent ratio of ventilation at maximal exercise to maximal voluntary ventilation at rest ranged from 86 to 94 per cent. These results show that the reduction of ventilatory capacity was the main factor decreasing the aerobic performance of our COPD patients. Maximal exercise tolerance (VO2 max) did not change after almitrine treatment. Negative factors like an increase in neuromuscular drive did not occur, and positive factors like an increase in PaO2 and oxygen transport had no critical influence on exercise performance in our ventilatory-limited COPD patients.