Aldo A M Lima

Publications (65)211 Total impact

• Article: "Barriers" to Child Development and Human Potential: The Case for Including the "Neglected Enteric Protozoa" (NEP) and Other Enteropathy-Associated Pathogens in the NTDs.

  Luther A Bartelt, Aldo A M Lima, Margaret Kosek, Pablo Peñataro Yori, Gwenyth Lee, Richard L Guerrant
  PLoS Neglected Tropical Diseases 04/2013; 7(4):e2125. · 4.69 Impact Factor
• Article: Prevalence of enteroaggregative Escherichia coli and its virulence-related genes in a case-control study among children from Northeastern Brazil.

  Ila F N Lima, Nadia Boisen, Josiane da S Quetz, Alexandre Havt, Eunice B Carvalho, Alberto M Soares, Noelia L Lima, Rosa M S Mota, James P Nataro, Richard L Guerrant, Aldo A M Lima
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  ABSTRACT: Enteroaggregative Escherichia coli (EAEC) is an important agent that causes endemic and epidemic diarrheal diseases worldwide. Several EAEC virulence-related genes (VRGs) have been described but their role in the clinical outcome of infection is not completely defined. This study investigated the prevalence of EAEC and potential associations of its VRGs with risk or protection to diarrheal diseases in children from urban communities in Northeastern Brazil. The case-control study included 166 children, which had their stools evaluated for the EAEC diagnostic genes (aaiC and aatA) using polymerase chain reaction (PCR). Positive samples were further analyzed by multiplex PCR to identify 18 VRGs. EAEC was found in the same proportion in both groups (41%). The plasmid-borne gene encoding a hexosyltransferase homolog (capU) was the most frequently detected (89.6%) followed by dispersin protein (aap, 58.2%), and EAEC HilA homolog (eilA, 57.8%). AAF/III fimbrial subunit (agg3A) was the gene observed in the lower frequency (1.5%). Plasmid-encoded toxin (pet) or AAF/II fimbrial subunit (aafA) was significantly associated with cases. AAF/IV fimbrial subunit (agg4A) or hypothetical plasmid-encoded hemolysin (orf61) was significantly more detected in controls compared to children with diarrhea. In addition, one set of genes in combination, aaiC and agg3/4C but lacking agg4A and orf61, was associated with diarrhea cases; and another one, orf61 in the absence of pet and aafA was correlated with control children. These data confirm a high prevalence, endemicity and heterogeneity of EAEC strains in underdeveloped urban areas of the world like Northeastern Brazil. Statistical correlation with cases and controls was seen with either isolated or combined sets of genes, suggesting that the pathophysiology of EAEC infection involve a complex and dynamic modulation of several VRGs.
  Journal of Medical Microbiology 02/2013; · 2.50 Impact Factor
• Article: Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning.

  Aldo A M Lima, Michelle P Kvalsund, Paula P E de Souza, Italo L Figueiredo, Alberto M Soares, Rosa M S Mota, Noélia L Lima, Relana C Pinkerton, Peter P Patrick, Richard L Guerrant, Reinaldo B Oriá
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  ABSTRACT: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children. The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.
  Clinics (São Paulo, Brazil) 01/2013; 68(3):351-8. · 1.59 Impact Factor
• Article: The impoverished gut-a triple burden of diarrhoea, stunting and chronic disease.

  Richard L Guerrant, Mark D Deboer, Sean R Moore, Rebecca J Scharf, Aldo A M Lima
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  ABSTRACT: More than one-fifth of the world's population live in extreme poverty, where a lack of safe water and adequate sanitation enables high rates of enteric infections and diarrhoea to continue unabated. Although oral rehydration therapy has greatly reduced diarrhoea-associated mortality, enteric infections still persist, disrupting intestinal absorptive and barrier functions and resulting in up to 43% of stunted growth, affecting one-fifth of children worldwide and one-third of children in developing countries. Diarrhoea in children from impoverished areas during their first 2 years might cause, on average, an 8 cm growth shortfall and 10 IQ point decrement by the time they are 7-9 years old. A child's height at their second birthday is therefore the best predictor of cognitive development or 'human capital'. To this 'double burden' of diarrhoea and malnutrition, data now suggest that children with stunted growth and repeated gut infections are also at increased risk of developing obesity and its associated comorbidities, resulting in a 'triple burden' of the impoverished gut. Here, we Review the growing evidence for this triple burden and potential mechanisms and interventions that must be understood and applied to prevent the loss of human potential and unaffordable societal costs caused by these vicious cycles of poverty.
  Nature Reviews Gastroenterology &#38 Hepatology 12/2012; · 8.10 Impact Factor
• Article: Arginine decreases Cryptosporidium parvum infection in undernourished suckling mice involving nitric oxide synthase and arginase.

  Ibraim C Castro, Bruna B Oliveira, Jacek J Slowikowski, Bruna P Coutinho, Francisco Júlio W S Siqueira, Lourrany B Costa, Jesus Emmanuel Sevilleja, Camila A Almeida, Aldo A M Lima, Cirle A Warren, Reinaldo B Oriá, Richard L Guerrant
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  ABSTRACT: This study investigated the role of L-arginine supplementation to undernourished and Cryptosporidium parvum-infected suckling mice. The following regimens were initiated on the fourth day of life and injected subcutaneously daily. The C. parvum-infected controls received L-arginine (200 mmol/L) or phosphate buffered saline. The L-arginine-treated mice were grouped to receive NG-nitro-arginine methyl ester (L-NAME) (20 mmol/L) or phosphate buffered saline. The infected mice received orally 10(6) excysted C. parvum oocysts on day 6 and were euthanized on day 14 at the infection peak. L-arginine improved weight gain compared with the untreated infected controls. L-NAME profoundly impaired body weight gain compared with all other groups. Cryptosporidiosis was associated with ileal crypt hyperplasia, villus blunting, and inflammation. L-arginine improved mucosal histology after the infection. L-NAME abrogated these arginine-induced improvements. The infected control mice showed an intense arginase expression, which was even greater with L-NAME. L-arginine decreased the parasite burden, an effect that was reversed by L-NAME. Cryptosporidium parvum infection increased urine NO(3)(-)/NO(2)(-) concentrations compared with the uninfected controls, which was increased by L-arginine supplementation, an effect that was also reversed by L-NAME. These findings show a protective role of L-arginine during C. parvum infection in undernourished mice, with involvement of arginase I and nitric oxide synthase enzymatic actions.
  Nutrition 01/2012; 28(6):678-85. · 3.03 Impact Factor
• Article: Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil.

  Sumeet S Mitter, Reinaldo B Oriá, Michelle P Kvalsund, Paula Pamplona, Emanuella Silva Joventino, Rosa M S Mota, Davi C Gonçalves, Peter D Patrick, Richard L Guerrant, Aldo A M Lima
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  ABSTRACT: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice weekly), or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-for-height z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6) later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. Thirty-seven children were apolipoprotein E4(+), with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+) children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+) children and improved delta lactulose/mannitol. Apolipoprotein E4(-) children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. During development, apolipoprotein E4 may function concomitantly with gut-tropic nutrients to benefit immediate nutritional status, which can translate into better long-term cognitive outcomes.
  Clinics (São Paulo, Brazil) 01/2012; 67(1):11-8. · 1.59 Impact Factor
• Article: Evidence for genetic susceptibility to developing early childhood diarrhea among shantytown children living in northeastern Brazil.

  Relana C Pinkerton, Reinaldo B Oriá, Jack W Kent, Anita Kohli, Claudia Abreu, Oluma Bushen, Aldo A M Lima, John Blangero, Sarah Williams-Blangero, Richard L Guerrant
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  ABSTRACT: To explore the genetic components of susceptibility to early childhood diarrhea (ECD), we used a quantitative genetic approach to estimate the heritability of ECD among children from two Brazilian favelas. Shared environment was used to model common exposure to environmental factors. Genetic relatedness was determined from pedigree information collected by screening household participants (n = 3,267) from two geographically related favelas located in Fortaleza, Brazil. There were 277 children within these pedigrees for whom diarrheal episodes in the first two years of life were recorded. Data on environmental exposure and pedigree relationship were combined to quantitatively partition phenotypic variance in ECD into environmental and genetic components by using a variance components approach as implemented in Sequential Oligogenic Linkage Analysis Routines program. Heritability accounted for 54% of variance in ECD and proximity of residence effect accounted for 21% (P < 0.0001). These findings suggest a substantial genetic component to ECD susceptibility and the potential importance of future genetics studies.
  The American journal of tropical medicine and hygiene 11/2011; 85(5):893-6. · 2.59 Impact Factor
• Article: Alanyl-glutamine promotes intestinal epithelial cell homeostasis in vitro and in a murine model of weanling undernutrition.

  Priscilla M Ueno, Reinaldo B Oriá, Elizabeth A Maier, Marjorie Guedes, Orleancio G de Azevedo, David Wu, Tara Willson, Simon P Hogan, Aldo A M Lima, Richard L Guerrant, D Brent Polk, Lee A Denson, Sean R Moore
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  ABSTRACT: Alanyl-glutamine (Ala-Gln) has recently been shown to enhance catch-up growth and gut integrity in undernourished children from Northeast Brazil. We hypothesized that the intestinal epithelial effects of Ala-Gln in malnourished weanling mice and mouse small intestinal epithelial (MSIE) cells would include modulation of barrier function, proliferation, and apoptosis. Dams of 10-day-old suckling C57BL/6 pups were randomized to a standard diet or an isocaloric Northeast Brazil "regional basic diet," moderately deficient in protein, fat, and minerals. Upon weaning to their dam's diet on day of life 21, pups were randomized to Ala-Gln solution or water. At 6 wk of age, mice were killed, and jejunal tissue was collected for morphology, immunohistochemistry, and Ussing chamber analysis of transmucosal resistance and permeability. Proliferation of MSIE cells in the presence or absence of Ala-Gln was measured by MTS and bromodeoxyuridine assays. MSIE apoptosis was assessed by annexin and 7-amino-actinomycin D staining. Pups of regional basic diet-fed dams exhibited failure to thrive. Jejunal specimens from undernourished weanlings showed decreased villous height and crypt depth, decreased transmucosal resistance, increased permeability to FITC-dextran, increased claudin-3 expression, and decreased epithelial proliferation and increased epithelial apoptosis (as measured by bromodeoxyuridine and cleaved caspase-3 staining, respectively). Undernourished weanlings supplemented with Ala-Gln showed improvements in weight velocity, villous height, crypt depth, transmucosal resistance, and epithelial proliferation/apoptosis compared with unsupplemented controls. Similarly, Ala-Gln increased proliferation and reduced apoptosis in MSIE cells. In summary, Ala-Gln promotes intestinal epithelial homeostasis in a mouse model of malnutrition-associated enteropathy, mimicking key features of the human disease.
  AJP Gastrointestinal and Liver Physiology 07/2011; 301(4):G612-22. · 3.43 Impact Factor
• Article: Cryptosporidium-malnutrition interactions: mucosal disruption, cytokines, and TLR signaling in a weaned murine model.

  Lourrany B Costa, Eric A JohnBull, Jordan T Reeves, Jesus Emmanuel Sevilleja, Rosemayre S Freire, Paul S Hoffman, Aldo A M Lima, Reinaldo B Oriá, James K Roche, Richard L Guerrant, Cirle Alcantara Warren
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  ABSTRACT: Cryptosporidiosis is a leading cause of persistent diarrhea in children in impoverished and developing countries and has both a short- and long-term impact on the growth and development of affected children. An animal model of cryptosporidial infection that mirrors closely the complex interaction between nutritional status and infection in children, particularly in vulnerable settings such as post-weaning and malnourishment, is needed to permit exploration of the pathogenic mechanisms involved. Weaned C57BL/6 mice received a protein-deficient (2%) diet for 3-12 days, then were infected with 5 × 10(7) excysted C. parvum oocyts, and followed for rate of growth, parasite stool shedding, and intestinal invasion/morphometry. Mice had about 20% reduction in weight gain over 12 days of malnutrition and an additional 20% weight loss after C. parvum challenge. Further, a significantly higher fecal C. parvum shedding was detected in malnourished infected mice compared to the nourished infected mice. Also, higher oocyst counts were found in ileum and colon tissue samples from malnourished infected mice, as well as a significant reduction in the villous height-crypt depth ratio in the ileum. Tissue Th1 cytokine concentrations in the ileum were significantly diminished by malnutrition and infection. mRNA for toll-like receptors 2 and 4 were diminished in malnourished infected mice. Treatment with nitazoxanide did not prevent weight loss or parasite stool shedding. These findings indicate that, in the weaned animal, malnutrition intensifies cryptosporidial infection, while cryptosporidial infection further impairs normal growth. Depressed TLR2 and 4 signaling and Th1 cytokine response may be important in the mechanisms underlying the vicious cycle of malnutrition and enteric infection.
  Journal of Parasitology 06/2011; 97(6):1113-20. · 1.40 Impact Factor
• Article: Infection: Preventing 5 million child deaths from diarrhea in the next 5 years.

  Sean R Moore, Aldo A M Lima, Richard L Guerrant
  Nature Reviews Gastroenterology &#38 Hepatology 01/2011; 8(7):363-4. · 8.10 Impact Factor
• Article: Prolonged episodes of acute diarrhea reduce growth and increase risk of persistent diarrhea in children.

  Sean R Moore, Noélia L Lima, Alberto M Soares, Reinaldo B Oriá, Relana C Pinkerton, Leah J Barrett, Richard L Guerrant, Aldo A M Lima
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  ABSTRACT: Prolonged episodes of acute diarrhea (ProD; duration 7-13 days) or persistent diarrhea (PD; duration ≥14 days) are important causes of undernutrition, yet the epidemiology and nutritional impact of ProD are poorly understood. We conducted a 10-year cohort study of 414 children from a Brazilian shantytown who were followed from birth; data were collected on diarrhea, enteric pathogens, and anthropometry. During 1276 child-years of observation, we recorded 3257 diarrheal episodes. ProD was twice as common as PD (12% and 5% of episodes, respectively); ProD and PD together accounted for 50% of all days with diarrhea. ProD was more common in infants whose mothers had not completed primary school (relative risk [RR], 2.1; 95% confidence interval: 1.02-2.78). Early weaning was associated with earlier onset of ProD (Spearman ρ = 0.309; P = .005). Infants with ProD were twice as likely to develop PD in later childhood (log rank, P = .002) compared with infants with only acute diarrhea (AD; duration <7 days), even after controlling for confounders. Children's growth was more severely stunted before their first episode of ProD, compared with AD (mean height-for-age Z score (HAZ) -0.81 vs -0.51, respectively, P < .05, unpaired t test). Following ProD, HAZ (ΔHAZ = -0.232) and weight-for-age (ΔWAZ = -0.26) significantly decreased (P < .005 in paired t tests). ProD was associated with Cryptosporidium and Shigella infections. ProD accounts for significant morbidity and identifies children at risk of a vicious cycle of diarrhea and malnutrition. Further studies are needed to address the recognition and control of ProD and its consequences in resource-limited settings and assess its role in PD pathogenesis.
  Gastroenterology 10/2010; 139(4):1156-64. · 11.68 Impact Factor
• Article: Effects of vitamin A supplementation on intestinal barrier function, growth, total parasitic, and specific Giardia spp infections in Brazilian children: a prospective randomized, double-blind, placebo-controlled trial.

  Aldo A M Lima, Alberto M Soares, Noélia L Lima, Rosa M S Mota, Bruna L L Maciel, Michelle P Kvalsund, Leah J Barrett, Relana P Fitzgerald, William S Blaner, Richard L Guerrant
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  ABSTRACT: This study evaluates the effects of retinol on intestinal barrier function, growth, total parasites, and Giardia spp infections in children in northeastern Brazil. The study was a double-blind, randomized placebo-controlled trial (http://clinicaltrials.gov; register no. #NCT00133406) involving 79 children who received vitamin A 100,000-200,000 IU (n = 39) or placebo (n = 40) at enrollment, 4, and 8 months and were followed for 36 months. Intestinal barrier function was evaluated using the lactulose:mannitol ratio test. Stool lactoferrin was used as a marker for intestinal inflammation. The groups were similar with regard to age, sex, nutritional parameters (z scores), serum retinol concentrations, proportion of lactoferrin-positive stool samples, and intestinal barrier function. The lactulose:mannitol ratio did not change during the same time of follow-up (P > 0.05). The proportion of lactoferrin-positive samples evaluated at 1 month did not change between groups (P > 0.05). Total intestinal parasitic, specifically new, infections were significantly lower in the vitamin A treatment compared with control group; these were accounted for entirely by significantly fewer new Giardia infections in the vitamin A treatment group. The cumulative z scores for weight-for-length or height, length or height-for-age z scores, and weight-for-age did not change significantly with vitamin A intervention for 36 months of follow-up. These data showed that total parasitic infection and Giardia spp infections were significantly lower in the vitamin A treatment group when compared with the placebo group, suggesting that vitamin A improves the host's defenses against Giardia infections.
  Journal of pediatric gastroenterology and nutrition 03/2010; 50(3):309-15. · 2.18 Impact Factor
• Source

  Available from: PubMed Central

  Article: Evaluation of HIV protease and nucleoside reverse transcriptase inhibitors on proliferation, necrosis, apoptosis in intestinal epithelial cells and electrolyte and water transport and epithelial barrier function in mice.

  Manuel B Braga Neto, Carolina V Aguiar, Jamilly G Maciel, Bruna M C Oliveira, Jesus E Sevilleja, Reinaldo B Oriá, Gerly A C Brito, Cirle A Warren, Richard L Guerrant, Aldo A M Lima
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  ABSTRACT: Protease inhibitors (PI's) and reverse transcriptase drugs are important components of highly active antiretroviral therapy (HAART) for treating human acquired immunodeficiency syndrome (AIDS). Long-term clinical therapeutic efficacy and treatment compliance of these agents have been limited by undesirable side-effects, such as diarrhea. This study aims to investigate the effects of selected antiretroviral agents on intestinal histopathology and function in vivo and on cell proliferation and death in vitro. Selected antiretroviral drugs were given orally over 7 days, to Swiss mice, as follows: 100 mg/kg of nelfinavir (NFV), indinavir (IDV), didanosine (DDI) or 50 mg/kg of zidovudine (AZT). Intestinal permeability measured by lactulose and mannitol assays; net water and electrolyte transport, in perfused intestinal segments; and small intestinal morphology and cell apoptosis were assessed in treated and control mice. In vitro cell proliferation was evaluated using the WST-1 reagent and apoptosis and necrosis by flow cytometry analysis. NFV, IDV, AZT and DDI caused significant reductions in duodenal and in jejunal villus length (p < 0.05). IDV and AZT increased crypt depth in the duodenum and AZT increased crypt depth in the jejunum. NFV, AZT and DDI significantly decreased ileal crypt depth. All selected antiretroviral drugs significantly increased net water secretion and electrolyte secretion, except for DDI, which did not alter water or chloride secretion. Additionally, only NFV significantly increased mannitol and lactulose absorption. NFV and IDV caused a significant reduction in cell proliferation in vitro at both 24 h and 48 h. DDI and AZT did not alter cell proliferation. There was a significant increase in apoptosis rates in IEC-6 cells after 24 h with 70 ug/mL of NFV (control: 4.7% vs NFV: 22%) while IDV, AZT and DDI did not show any significant changes in apoptosis compared to the control group. In jejunal sections, IDV and NFV significantly increased the number of TUNEL positive cells. The PI's, NFV and IDV, increased cell apoptosis in vivo, water and electrolyte secretion and intestinal permeability and decreased villus length and cell proliferation. NFV was the only drug tested that increased cell apoptosis in vitro. The nucleoside reverse transcriptase inhibitors, AZT and DDI, did not affect cell apoptosis or proliferation. These findings may partly explain the intestinal side-effects associated with PI's.
  BMC Gastroenterology 01/2010; 10:90. · 2.42 Impact Factor
• Article: Serum concentrations of rifampin, isoniazid, and intestinal absorption, permeability in patients with multidrug resistant tuberculosis.

  Elizabeth C Barroso, Valéria G F Pinheiro, Mônica C Façanha, Maria R D Carvalho, Maria E Moura, Creusa L Campelo, Charles A Peloquin, Richard L Guerrant, Aldo A M Lima
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  ABSTRACT: This study evaluates the serum concentrations of rifampin (RMP), isoniazid (INH), and intestinal barrier function in patients with multidrug-resistant tuberculosis (MDR-TB), drug susceptible tuberculosis (DS-TB), and health volunteers (HC; controls). Peak serum concentrations of RMP were significantly lower in MDR-TB and DS-TB as compared with HC (odds ratio [OR] = 3.125, confidence interval [CI] [1.037-9.418] and OR = 4.025, CI [1.207-13.418], respectively). The INH peak serum concentration was not significantly different between MDR-TB versus DS-TB or DS-TB versus HC. The percent of mannitol excretion was significantly lower in the MDR-TB group compared with DS-TB (13.18 versus 16.03, analysis of covariance [ANCOVA], P = 0.0369) and compared with HC (13.18 versus 16.61, ANCOVA, P = 0.0291) the other study groups. These data suggested a lower peak serum concentration of RMP for both MDR-TB and DS-TB as compared with the HC group. The data also showed a lower intestinal area of absorption in patients with tuberculosis and even worse in MDR-TB.
  The American journal of tropical medicine and hygiene 09/2009; 81(2):322-9. · 2.59 Impact Factor
• Article: Semantic fluency: a sensitive marker for cognitive impairment in children with heavy diarrhea burdens?

  Reinaldo B Oriá, Carlos Maurício C Costa, Aldo A M Lima, Peter D Patrick, Richard L Guerrant
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  ABSTRACT: One of the most affected cognitive impairments in children who experienced heavy burdens of diarrhea is semantic fluency, the same impairment that is most affected in Alzheimer's dementia. These findings are leading us into provocative genetic studies that may elucidate the evolution of such genetic polymorphisms as the APOE alleles. Alternatively, diarrhea could launch the cognitive deficits that might later progress in neurodegenerative diseases. In addition, they suggest that semantic fluency could provide a simple mean to assess cognitive impairment in impoverished settings so as to determine preventive measures.
  Medical Hypotheses 07/2009; 73(5):682-6. · 1.39 Impact Factor
• Article: High-salt intake primes the rat kidney to respond to a subthreshold uroguanylin dose during ex vivo renal perfusion.

  Manassés C Fonteles, A Havt, Rodrigo B Prata, Patrícia H B Prata, Helena S A Monteiro, Aldo A M Lima, Antônio R C Jorge, Cláudia F Santos, Richard N Greenberg, Nilberto R F Nascimento
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  ABSTRACT: In a variety of animal models, uroguanylin causes diuresis, natriuresis and kaliuresis and is found in larger concentrations in the urine compared to controls after oral salt intake or in conditions of excess salt and fluid retention. It has been proposed that uroguanylin functions as an intestinal natriuretic hormone following intake of meals high in salt content. In the present work, we examined if 10 days of salt ingestion resulted in an enhanced response to uroguanylin in the isolated perfused rat kidney. Rats were given normal water, 1% NaCl (HS1%), or 2% NaCl (HS2%) for 10 days, at which time the right kidneys were surgically removed and perfused with a modified Krebs-Henseleit solution for 30 min. After a 30-min control period, the kidneys were perfused with a modified Krebs-Henseleit solution containing 0.06 microM uroguanylin for an additional 90 min. Compared to vehicle-matched time controls, 0.06 microM uroguanylin perfusion of kidneys from rats maintained on HS2% resulted in a significantly increased urine flow (UF; from 0.17+/-0.01 to 0.23+/-0.01, after 60 min, n=6, P<0.05), fractional Na(+) excretion (%E(Na+); from 16.6+/-0.7 to 30+/-2, after 60 min, n=6, P<0.05), fractional K(+) excretion (%E(K+); from 20.5+/-0.58 to 37.4+/-2.1, after 60 min, n=6, P<0.05), and fractional Cl(-) excretion increased from 18.16+/-0.52 to 35.2+/-2.0 at 60 min, n=6, P<0.05. With the exception of a significant increase in the %E(K)(+), no other effect was observed in the kidneys from the rats maintained on HS1%, and no significant effects were seen in those that were maintained on normal water. The effect of a higher dose (0.6 microM) of uroguanylin on urinary flow, sodium or potassium excretion was also significantly increased by 2% NaCl (HS2%) treatment (P<0.05). We also observed an expressive upregulation of the GC-C and a slight downregulation of the GC-A receptor in high-salt treated rats. These data demonstrate that prolonged salt ingestion primes the kidney to enhanced renal responses to uroguanylin.
  Regulatory Peptides 07/2009; 158(1-3):6-13. · 2.11 Impact Factor
• Article: Faecal contamination of drinking water in a Brazilian shanty town: importance of household storage and new human faecal marker testing.

  Curtis C Copeland, Benjamin B Beers, Meghan R Thompson, Relana P Fitzgerald, Leah J Barrett, Jesus E Sevilleja, Sayonara Alencar, Aldo A M Lima, Richard L Guerrant
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  ABSTRACT: Worldwide, contaminated drinking water poses a major health threat, particularly to child development. Diarrhoea represents a large part of the water-related disease burden and enteric infections have been linked to nutritional and growth shortfalls as well as long-term physical and cognitive impairment in children. Previous studies detailed the frequency of infection and the consequences for child health in a shanty town in north-east Brazil. To determine the frequency of contaminated water, we measured faecal contamination in primary drinking water samples from 231 randomly selected households. Risk for contamination was compared across source and storage types. Nearly a third of the study households (70/231: 30.3%) had contaminated drinking water; the source with the highest frequency of contamination was well water (23/24: 95.8%). For tap water, the type of storage had a significant effect on the susceptibility to contamination (chi(2) = 12.090; p = 0.007). The observed pattern of contamination demonstrated the relative potential contributions of both source and storage. With evidence that supports the inclusion of source and storage in water quality surveys, this study, like others, suggests that contaminated drinking water in storage vessels may be an important factor for the documented diarrhoea disease burden in the Brazilian shanty town.
  Journal of Water and Health 07/2009; 7(2):324-31. · 1.37 Impact Factor
• Article: Intestinal barrier function and serum concentrations of rifampin, isoniazid and pyrazinamide in patients with pulmonary tuberculosis.

  Mônica C Façanha, Argina M B Gondim, Valéria G F Pinheiro, Elizabeth C Barroso, Charles A Peloquin, Richard L Guerrant, Aldo A M Lima
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  ABSTRACT: Intestinal barrier function and serum concentrations of rifampin, isoniazid and pyrazinamide were studied in healthy controls and patients with active pulmonary tuberculosis. A case-control study of 29 controls and 30 cases attending at the Health Center, July, 2004 to December, 2005 was conducted. The body mass index was significantly reduced in cases compared to controls (p < 0.001). The intestinal paracellular transport of lactulose was significantly (p = 0.019) reduced in cases compared to controls. The transcellular transport of mannitol and the lactulose:mannitol ratio were not significantly (p = 0.0698) reduced in cases compared to controls. Low serum concentrations of rifampin, isoniazid and pyrazinamide were observed in 81% (48/59), 92% (54/59) and 28% (12/59), respectively, in all individuals. The results demonstrated a marked decrease on intestinal paracellular transport in patients with active pulmonary tuberculosis and reduced serum concentrations of rifampin and isoniazid in both groups.
  The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 06/2009; 13(3):210-7. · 0.55 Impact Factor
• Article: Carotenoids, retinol, and intestinal barrier function in children from northeastern Brazil.

  Milena M Vieira, Jisun Paik, William S Blaner, Alberto M Soares, Rosa M S Mota, Richard L Guerrant, Aldo A M Lima
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  ABSTRACT: To investigate the association of carotenoids and retinol (vitamin A) with intestinal barrier function in children in an urban community in Fortaleza, northeastern Brazil. Descriptive analysis of serum carotenoids and retinol concentrations with intestinal barrier function in 102 children from an urban community, July 2000 to August 2001. The weight for height z score (wasting) showed that 19.6% (20/102) had mild malnutrition (-1 to -2 z score). All of the children's serum retinol concentrations were determined and none were severely deficient (< or =0.35 micromol/L), 2.9% (3/102) were moderately (0.36-0.70 micromol/L) deficient, 20.6% (21/102) were mildly (0.71-1.05 micromol/L) deficient; 76.5% (78/102) were vitamin A sufficient (>1.05 micromol/L). The lactulose:mannitol (L/M) ratio was elevated (> or =0.0864) in 49% (47/97) of children when compared with healthy children with normal L/M ratio (<0.0864) in the same geographic area. Serum carotenoids, lutein, beta-cryptoxanthin and beta-carotene showed significant inverse correlations with the L/M ratio, but not lutein after adjusting for age. Acute phase proteins (C-reactive protein and alpha-acid glycoprotein) were significantly inversely correlated with retinol but not with carotenoids. Retinol and retinol-binding protein were not significantly associated with L/M ratio. These data suggest a disruption of intestinal barrier function in the paracellular pathway with low serum concentrations of carotenoids. Carotenoids may provide a better marker for disrupted intestinal barrier function than retinol-binding protein or retinol.
  Journal of pediatric gastroenterology and nutrition 11/2008; 47(5):652-9. · 2.18 Impact Factor
• Article: Malnutrition as an enteric infectious disease with long-term effects on child development.

  Richard L Guerrant, Reinaldo B Oriá, Sean R Moore, Mônica O B Oriá, Aldo A M Lima
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  ABSTRACT: Malnutrition is a major contributor to mortality and is increasingly recognized as a cause of potentially lifelong functional disability. Yet, a rate-limiting step in achieving normal nutrition may be impaired absorptive function due to multiple repeated enteric infections. This is especially problematic in children whose diets are marginal. In malnourished individuals, the infections are even more devastating. This review documents the evidence that intestinal infections lead to malnutrition and that malnutrition worsens intestinal infections. The clinical data presented here derive largely from long-term cohort studies that are supported by controlled animal studies. Also reviewed are the mechanisms by which enteric infections lead to undernutrition and by which malnutrition worsens enteric infections, with implications for potential novel interventions. Further intervention studies are needed to document the relevance of these mechanisms and, most importantly, to interrupt the vicious diarrhea-malnutrition cycle so children may develop their full potential.
  Nutrition Reviews 10/2008; 66(9):487-505. · 4.47 Impact Factor