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Biomedical subjects

A A Lima

Publications and source records attributed to A A Lima.

At least 19 recordsLinked to original sources

Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto study.

The influence of apolipoprotein E alleles and genotypes on plasma lipid levels was determined in 185 individuals of mixed ethnicity living in Ouro Preto, Brazil. DNA was obtained from blood samples and the genotypes were determined by an RFLP-PCR procedure. The *3 allele was the most frequent (72%), followed by *4 (20%) and *2 (8%); *4 frequency was higher and *2 frequency was lower in the dyslipidemic group than in the normal control group. The *2 carriers presented lower LDL and total cholesterol levels compared to the *3 and *4 carriers. All six expected genotypes were observed in the individuals genotyped: E2/2 (2.1%), E4/4 (2.7%), E2/4 (3.7%), E2/3 (8.0%), E3/3 (53.3%), E3/4 (29.9%); no difference in genotype frequencies was found between the normal and dyslipidemic groups. Compared with *2, the presence of *3 increases more than two times the risk for dyslipidemia (OR = 2.31; P = 0.025; 95% CI = 1.06-5.06) and the presence of *4 increases it three times (OR = 3.31; P = 0.006; 95% CI = 1.36-8.04). The only significant effect of genotype was an increased risk for dyslipidemia in the *4 genotype carriers (E3/4 + E4/4) compared with the *2 genotype carriers (E2/2 + E2/3) with OR = 3.69 (95% CI = 1.25-10.88). The present study indicates that in the Ouro Preto admixed population the presence of APOE *2 can confer a protective effect, whereas the presence of APOE *4 implies an enhanced risk for dyslipidemia.

Apolipoprotein E3↗

Hepatitis C virus infection among Brazilian hemophiliacs: a virological, clinical and epidemiological study.

We determined and analyzed risk factors of hepatitis C virus (HCV)-infected Brazilian hemophiliacs according to their virological, clinical and epidemiological characteristics. A cross-sectional and retrospective study of 469 hemophiliacs was carried out at a Brazilian blood center starting in October 1997. The prevalence of HCV infection, HCV genotypes and factors associated with HCV RNA detection was determined. The seroprevalence of anti-HCV antibodies (ELISA-3.0) was 44.6% (209/469). Virological, clinical and epidemiological assessments were completed for 162 positive patients. There were seven (4.3%) anti-HCV seroconversions between October 1992 and October 1997. During the same period, 40.8% of the positive anti-HCV hemophiliacs had abnormal alanine transaminase (ALT) levels. Plasma HCV RNA was detected by nested-RT-PCR in 116 patients (71.6%). RFLP analysis showed the following genotype distribution: HCV-1 in 98 hemophiliacs (84.5%), HCV-3 in ten (8.6%), HCV-4 in three (2.6%), HCV-2 in one (0.9%), and not typeable in four cases (3.4%). Univariate analysis indicated that older age (P = 0.017) and abnormal ALT levels (P = 0.010) were associated with HCV viremia, while the presence of inhibitor antibodies (P = 0.024) and HBsAg (P = 0.007) represented a protective factor against the presence of HCV RNA. These findings may contribute to a better understanding of the relationship between HCV infection and hemophilia.

Adult↗

Dual effect of cAMP on the writhing response in mice.

The intraperitoneal injection of agents that increase the intracellular level of cyclic AMP (cAMP), reduced significantly the number of writhes induced by acetic acid and zymosan in mice. However, dibutyryl cyclic AMP (Db-cAMP) induced a dual response: (a) low doses caused antinociception, and (b) a high dose potentiated the nociceptive effect of a low concentration of acetic acid. High doses of Db-cAMP also reversed the antinociceptive effect of dexamethasone and the depletion of resident peritoneal cells. We also demonstrated that a low dose of Db-cAMP, forskolin or dexamethasone inhibited the production of tumor necrosis factor-alpha and interleukin-1 beta by macrophages stimulated by zymosan. In conclusion, this study suggests that cAMP has a dual effect in the writhing model: an antinociceptive effect due to its modulatory action on resident peritoneal cells, thus, reducing the synthesis of mediators involved in the nociceptive response, and a nociceptive effect by directly sensitizing the nociceptive neuron.

Acetic Acid↗

Cryptosporidiosis: an update.

Cryptosporidiosis was recognised in human beings in 1976, and was prominent in the 1980s and 1990s as a cause of severe diarrhoeal illness in patients with AIDS. It is now additionally recognised as a major cause of waterborne diarrhoeal illness in developed regions, and as a pathogen with long-term effect on childhood growth and development in impoverished areas. This update focuses on recent changes in our understanding of the taxonomy of cryptosporidium, its epidemiology, effects, pathogenesis, diagnosis, and treatment.

Animals↗

A longitudinal study of Giardia lamblia infection in north-east Brazilian children.

OBJECTIVE: To evaluate the epidemiology of Giardia lamblia infection, investigate factors which might be associated with clinical manifestations and recurrence, and examine the role of copathogens in disease course. METHODS: Prospective 4-year cohort study of children born in an urban slum in north-eastern Brazil. RESULTS: Of 157 children followed for > or = 3 months, 43 (27.4%) were infected with Giardia. The organism was identified in 8.8% of all stool specimens, and although found with similar frequency in non-diarrhoeal (7.4%) and diarrhoeal stools (9.7%), was more common in children with persistent (20.6%) than acute diarrhoea (7.6%, P=0.002). Recurrent or relapsing infections were common (46%). Children with symptomatic infections had significantly lower weight-for-age and height-for-age than asymptomatic children. Copathogens were not associated with disease course. CONCLUSION With its protean clinical manifestations, Giardia may be associated with substantial morbidity amongst children in Brazil.

Animals↗

Early childhood diarrhoea and helminthiases associate with long-term linear growth faltering.

BACKGROUND: Although the acute mortality from diarrhoeal diseases is well recognized, the potentially prolonged impact of early childhood diarrhoea on background growth and development is often overlooked. To examine the magnitude and duration of the association of early childhood enteric infections with growth faltering in later childhood, we investigated associations of early childhood diarrhoea (0-2 years) and intestinal helminthiases with nutritional status from age 2 to 7 years. METHODS: Twice-weekly diarrhoea surveillance and quarterly anthropometrics were followed from 1989 to 1998 in 119 children born into a Northeast Brazilian shantytown. RESULTS: Diarrhoea burdens at 0-2 years old were significantly associated with growth faltering at ages 2-7 years, even after controlling for nutritional status in infancy, helminthiases at 0-2 years old, family income, and maternal education by Pearson correlation, multivariate linear regression, and repeat measures analysis. The average 9.1 diarrhoeal episodes before age 2 years was associated with a 3.6 cm (95% CI : 0.6-6.6 cm) growth shortfall at age 7 years. Early childhood helminthiasis was also associated with linear growth faltering and a further 4.6 cm shortfall (95% CI : 0.8-7.9 cm) at age 7 years. CONCLUSIONS: Early childhood diarrhoea and helminthiases independently associate with substantial linear growth shortfalls that continue beyond age 6 years. Targeted interventions for their control may have profound and lasting growth benefits for children in similar settings.

Anthropometry↗

Tropical diarrhoea: new developments in traveller's diarrhoea.

Traveller's diarrhoea is the most common illness acquired by visitors to developing countries, affecting 20-50% of the 35 million people who travel from industrialized countries each year. Important risk factors include point of origin and destination of the traveller, host factors, and exposure to contaminated food and water. The most common causes of traveller's diarrhoea in adults in developing countries include infection with Escherichia coli, Shigella spp., Salmonella spp., Campylobacter spp., Vibrio parahaemolyticus (in Asia), rotavirus (in Latin America), and protozoa (Giardia, Cryptosporidium and Cyclospora spp., and Entamoeba histolytica). No pathogen is identified in over half of patients with traveller's diarrhoea, however. The primary objectives of treatment of traveller's diarrhoea are to reduce the symptoms and duration of diarrhoeal illness, to reduce inconvenience caused by such illness and to prevent cancellation of planned activities. These important objectives are best accomplished by empirical self-therapy with a combination of antimicrobial agents and loperamide. Since the first use of ciprofloxacin, fluoroquinolones have become the drugs of choice in empirical therapy for moderate-to-severe traveller's diarrhoea in adults. The options for children include nalidixic acid, trimethoprim-sulfamethoxazole (along with erythromycin if Campylobacter infection is a possibility) and furazolidone. Education on hygiene and safe food preparation help to prevent many diarrhoeal diseases, including traveller's diarrhoea.

Anti-Bacterial Agents↗

The effect of tumour necrosis factor (TNF) inhibitors in Clostridium difficile toxin-induced paw oedema and neutrophil migration.

Clostridium difficile produces a potent enterotoxin and a cytotoxin, toxin A and toxin B, respectively. These toxins are associated with pseudomembranous colitis and antibiotic-associated diarrhoea. In the present study, we investigated the oedematogenic activity of both toxins, characterizing the time-course and dose-response of this pro-inflammatory event. We also explored the effects of two inhibitors of tumour necrosis factor (TNF) production, thalidomide and pentoxifylline, in neutrophil recruitment and the oedematogenic activity of these toxins. Subplantar injection of toxin A induced paw oedema with a maximal response at 1 microg, reaching a maximal value 9 hr after toxin A challenge (toxin A 1 microg:1.39+/-0.09 ml). Toxin B also showed a dose-dependent oedematogenic activity with a late peak at 24 hr and a maximal response at a dose of 0.1 microg (toxin B 0.1 microg:1.74+/-0.12 ml). Pentoxifylline, but not thalidomide, significantly reduced the oedema induced by Toxin A (pentoxifylline 135 mg/kg:60% of inhibition) and Toxin B (pentoxifylline 135 mg/kg:33.6% of inhibition). Both thalidomide and pentoxifylline were able to significantly reduce neutrophil influx into the peritoneal cavities of rats evoked with Toxin A (thalidomide 45 mg/kg: 53.1% of inhibition; pentoxifylline 45 mg/kg:47.1% of inhibition) and Toxin B (thalidomide 45 mg/kg:46.8% of inhibition; pentoxifylline 45 mg/kg:63.1% of inhibition). This study demonstrates the oedematogenic activities of both toxins with distinct potencies and time-courses. These data also show an inhibitory effect of pentoxifylline in toxin A and B-induced paw oedema. Furthermore, both pentoxifylline and thalidomide significantly inhibited the Clostridium difficile toxins-induced neutrophil migration.

Animals↗

Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: a prospective cohort study among children in northeastern Brazil.

Persistent diarrhea (PD; duration >/=14 days) is a growing part of the global burden of diarrheal diseases. A 45-month prospective cohort study (with illness, nutritional, and microbiologic surveillance) was conducted in a shantytown in northeastern Brazil, to elucidate the epidemiology, nutritional impact, and causes of PD in early childhood (0-3 years of age). A nested case-control design was used to examine children's diarrhea burden and nutritional status before and after a first PD illness. PD illnesses accounted for 8% of episodes and 34% of days of diarrhea. First PD illnesses were preceded by a doubling of acute diarrhea burdens, were followed by further 2.6-3.5-fold increased diarrhea burdens for 18 months, and were associated with acute weight shortfalls. Exclusively breast-fed children had 8-fold lower diarrhea rates than did weaned children. PD-associated etiologic agents included Cryptosporidium, Giardia, enteric adenoviruses, and enterotoxigenic Escherichia coli. PD signals growth shortfalls and increased diarrhea burdens; children with PD merit extended support, and the illness warrants further study to elucidate its prevention, treatment, and impact.

Bacterial Infections↗

Seroprevalence and seroincidence of Norwalk-like virus infection among Brazilian infants and children.

To determine the importance of Norwalk-like viruses (NLVs) as pediatric pathogens in a developing country, the seroprevalence and seroincidence of this group of viruses in a cohort of children less than 4 years of age in an urban shantytown in northeastern Brazil was examined. Serum samples were collected approximately every 6 months from 135 children who were surveyed three times each week for diarrhea and vomiting. NLV IgG was measured by an enzyme immunosorbent assay (EIA) with recombinant Norwalk virus capsid protein. Overall NLV seroprevalence was 71%, and the overall NLV seroconversion rate was 0.7 seroconversions per child-year. The highest age-specific NLV seroconversion rate (0.8 seroconversions per child-year) was observed in the 13-24-month age group. For all study children, the incidence of diarrhea and vomiting was significantly greater (P < 0.01) during time periods spanned by serum pairs that indicated NLV seroconversion compared with time periods without NLV seroconversion. However, NLV seroconversion was not associated with gastrointestinal symptoms during the first year of life.

Brazil↗

Effects of pentoxifylline and nabumetone on the serum levels of IL-1beta and TNFalpha in rats with adjuvant arthritis.

OBJECTIVE AND DESIGN: This study examined whether serum levels of cytokines, IL-1beta and TNFalpha were elevated in rats with adjuvant arthritis in relation to disease progression, and if so, to verify the treatment effects of nabumetone (20 mg/kg, p. o.), a COX-2 inhibitor and pentoxifylline (20 mg/kg, p.o.), a type-4 phosphodiesterase (PDE4) inhibitor, alone or in combination. MATERIALS AND METHODS: Female Wistar rats were used. Freund's complete adjuvant (FCA) was used to induce arthritis. The increment in contralateral hind paw volume (the secondary lesion) was determined by plethysmometry and the serum cytokines were measured by ELISA. RESULTS: In control rats, the serum IL-1beta and TNFalpha levels were greatly elevated on the very first day i.e. 5 h after FCA, and thereupon a progressive decrease in IL-1beta but not TNFalpha was observed until day 30. The secondary arthritic lesion began to increase on day 14 (125+/-26 microl), and attained its peak (330+/-79 microl) on day 21 post-adjuvant injection. The peak arthritic lesion was significantly (p<0.001) less in rats that received nabumetone and pentoxifylline, alone or in combination (20+/-8, 41+/-15 and 65+/-10 microL, respectively). When serum cytokine levels were analysed on day 20 postadjuvant injection, rats treated with pentoxifylline or in association with nabumetone, but not nabumetone alone showed significantly lowered levels of serum TNFalpha. Unlike TNFalpha, serum IL-1beta did not vary significantly. CONCLUSIONS: The drugs nabumetone and pentoxifylline although appearing to produce differential effects on serum cytokine levels, seem to be equally efficacious in attentuating the progression of FCA-induced arthritis. Serum cytokine levels may not accurately reflect the treatment efficacy.

Animals↗

Changes over time in the epidemiology of diarrhea and malnutrition among children in an urban Brazilian shantytown, 1989 to 1996.

BACKGROUND: Endemic diarrhea and its associated malnutrition remain leading causes of childhood morbidity and mortality in developing countries. This study was undertaken to describe changes in the incidence of diarrhea and prevalence of malnutrition among children in an urban Brazilian shantytown from 1989 to 1996. A secondary purpose was to examine associations between malnutrition and increased incidence and duration of diarrhea. METHODS: From August 1989 through December 1996 a dynamic birth cohort of 315 children was followed for surveillance of diarrhea and nutrition. Study homes were visited twice or thrice weekly to assess the occurrence of diarrhea. Length and weight of the subjects were measured quarterly. Poisson regression was used to test for associations between prior nutritional status and subsequent diarrhea during a quarter. Multiple regression was used to test for an association between nutritional status and episode duration. RESULTS: Declines in both age-adjusted attack rates (6.0 episodes/child-year in study year 3 [1991] to 2.5 episodes per child-year in study year 8 [1996] and days of diarrhea per child-year (30.8 days/child-year in year 3 to 8.5 days/child-year in year 8) were correlated with yearly improvements in mean nutritional status (R2= 0.84, P < 0.05, for mean length-for-age with mean number of episodes/child-year [corrected]. Both length- and weight-for-age were significant predictors of diarrhea incidence, including persistent episodes (> or =14 d), but not duration. CONCLUSIONS: These results demonstrate marked changes over time in the diarrhea burden and nutritional status of children in this population and provide further evidence of a significant association between malnutrition and increased incidence of diarrhea.

Brazil↗

Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins.

Vitamin A (retinol) is required to maintain immunity and epithelial turnover and is a key micronutrient needed for combating infection. Vitamin A actions on the immune system are diverse and cannot be accounted for by a single effect or mechanism. The actions of retinol in maintaining gut integrity in humans and immunoglobulin levels in mice was investigated. For 30 children, performance on the lactulose/mannitol test, a test commonly used to assess intestinal barrier function, was inversely correlated (P=.012) with serum retinol concentrations. Thus, children with lower serum retinol, and presumably poorer vitamin A nutritional status, are more likely to have impaired intestinal integrity. Knockout mice that have impairments in plasma retinol transport have circulating immunoglobulin levels that are half those observed in matched wild type mice. No differences were observed in B and T cell populations present in spleen, thymus, and bone marrow.

Animals↗

Micronutrients and infection: interactions and implications with enteric and other infections and future priorities.

Symposium presentations have focused on the elegant molecular science and the biologic mechanisms by which micronutrients play critical roles in cellular and humoral immune responses, cellular signaling and function, and even in the evolution of microbial virulence. The concluding session examined the practical issues of how best to evaluate the nutritionally at-risk host, especially in the areas of greatest need-an analytical model of nutrient-immune interactions, implications of nutritional modulation of the immune response for disease, and the implications for international research and child health. This overview illustrated how malnutrition may be a major consequence of early childhood diarrhea and enteric infections, as enteric infections may critically impair intestinal absorptive function with potential long-term consequences for growth and development. The potentially huge, largely undefined DALY (disability-adjusted life years) impact of early childhood diarrheal illnesses demonstrates the importance of quantifying the long-term functional impact of largely preventable nutritional and infectious diseases, especially in children in developing areas.

Child↗

Supernatants from macrophages stimulated with microcystin-LR induce electrogenic intestinal response in rabbit ileum.

Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. This microorganism often forms toxic blooms in freshwater lakes and reservoirs for drinking water supply, producing serious disorders in humans and animals. Some have suggested that certain biological activities of microcystin may depend upon the stimulation of immune cells. Therefore, the aims of this research were to examine electrogenic intestinal secretion, in vitro, caused by the supernatants from macrophages stimulated with microcystin-LR, as well as to investigate the presence of interleukin-1beta and tumour necrosis factor-alpha in these supernatants. We found that the supernatants of macrophages stimulated with microcystin-LR (0.1, 0.3 and 1.0 microg/ml) caused electrogenic intestinal effects (change in short circuit currents (delta SCC)=57.6, 50.8 and 73.3, respectively, versus control=19.6 microA.cm(-2)) in a time-dependent way (microcystin-LR (1.0 microg/ml)=63.2, 108.8, 120.4 and 132.3 microA.cm(-2) at time 0, 40, 50 and 60 min., respectively). In addition, the intestinal secretory activity present in these supernatants was blocked (57%) by the prior treatment of macrophages with dexamethasone. We also demonstrated that microcystin-LR (0.1, 0.3 and 1.0 ,microg/ml) is capable of stimulating the synthesis of tumour necrosis factor-alpha (375.4, 369.0 and 610.8 pg/ml, respectively, versus control=165.0 pg/ml) and interleukin-1beta (198.9, 189.3 and 522.1 pg/ml, respectively, versus control=39.7 pg/ml). These findings demonstrate that microcystin-LR induces the release of interleukin-1beta and tumour necrosis factor-alpha by peritoneal macrophages in vitro, and that the supernatants from these macrophages induce electrogenic secretion in rabbit ileal mucosa.

Animals↗

Mechanisms and impact of enteric infections.

The increased recognition of both old and new enteric pathogens and their potential impact requires an improved understanding of pathogenesis and effective interventions. While the overwhelming mortality (> 3 million children per year) due to diarrheal diseases is well-recognized, the potential long-term impacts of enteric infections and early childhood diarrhea morbidity are just beginning to be appreciated. Furthermore, several enteric infections are now being recognized as causes of growth shortfalls with or without diarrhea; i.e., malnutrition may be one of the greatest yet of the "emerging infectious diseases." The increased appreciation of this extended impact calls for further quantification and improved understanding of the deranged physiology. In particular, persistent diarrheal illnesses exhibit common themes of blunted villi, disruption of intestinal barrier function and varying degrees of sub-mucosal inflammation for which lactulose/mannitol permeability and fecal lactoferrin provide respective quantification. Finally, such improved understanding will allow targeted interventions among those most vulnerable, which will enable further documentation of cost effectiveness and the potential for improved human development which is critical to reducing the widening disparity and population overgrowth which increasingly threaten our global security.

Animals↗

Longitudinal study of Cryptosporidium infection in children in northeastern Brazil.

A prospective, 4-year cohort study of children born in an urban slum in northeastern Brazil was undertaken to elucidate the epidemiology of Cryptosporidium infection in an endemic setting, describe factors associated with Cryptosporidium-associated persistent diarrhea, and clarify the importance of copathogens in symptomatic cryptosporidiosis. A total of 1476 episodes of diarrhea, accounting for 7581 days of illness (5.25 episodes/child-year), were recorded: of these, 102 episodes (6.9%) were persistent. Cryptosporidium oocysts were identified in 7.4% of all stools, and they were found more frequently in children with persistent diarrhea (16.5%) than in those with acute (8.4%) or no (4.0%) diarrhea (P<.001). Low-birth-weight children and those living in densely crowded subdivisions were at greater risk for symptomatic infection. Disease course was highly variable and was not associated with the presence of copathogens. Recurrent Cryptosporidium infection and relapsing diarrhea associated with it were moderately common. In light of these data, the applicability of the current World Health Organization diarrheal definitions to Cryptosporidium-associated diarrheal episodes may need to be reconsidered.

Analysis of Variance↗