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Biomedical subjects

Guillermo M Ruiz-Palacios

Publications and source records attributed to Guillermo M Ruiz-Palacios.

14 recordsLinked to original sources
PubMed2006

Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

Administration, Oral↗
PubMed2006

Adiponectin is present in human milk and is associated with maternal factors.

BACKGROUND: Previous studies have shown that human milk has a role in the gastrointestinal, neural, and immune development of neonates. If present in milk, adiponectin would be a promising candidate for influencing infant development, given its metabolic functions. OBJECTIVES: Our objectives were to determine whether adiponectin is present in human milk and to characterize maternal factors associated with potential variation in milk adiponectin concentrations. DESIGN: We quantified adiponectin concentrations in human milk samples from donors to the Cincinnati Children's Research Human Milk Bank and randomly selected participants in a cohort study in Mexico City funded by the National Institutes of Health. Using cross-sectional and longitudinal data, we examined milk adiponectin concentrations in relation to lactation duration, maternal body mass index (BMI; in kg/m(2)), and ethnicity. RESULTS: Adiponectin was detected in human skim milk (range: 4.2-87.9 ng/mL). In cross-sectional and longitudinal analyses, duration of lactation was negatively associated with milk adiponectin concentrations (beta = -0.059 +/- 0.024 and -0.059 +/- 0.007, respectively; P < 0.02 for both). Maternal postpregnancy BMI was positively associated with milk adiponectin concentrations (beta = 0.08 +/- 0.02, P < 0.0001; longitudinal analysis). Mexican mothers had lower median milk adiponectin concentrations at 1 mo than did the non-Hispanic white subjects from Cincinnati (11.5 and 19.8 ng/mL; P = 0.003). CONCLUSIONS: Adiponectin is present in human milk and its concentrations are associated with duration of lactation, maternal adiposity, and ethnicity. Given the importance of adiponectin in inflammation, insulin sensitivity, and fatty acid metabolism, future studies should examine milk adiponectin's role in infant metabolic development.

Adiponectin↗
PubMed2006

Risk of infant anemia is associated with exclusive breast-feeding and maternal anemia in a Mexican cohort.

The WHO recommends exclusive breast-feeding (EBF) for the first 6 mo of life to decrease the burden of infectious disease. However, some are concerned about the effect of EBF >6 mo on iron status of children in developing countries in which anemia is prevalent. This study examines the risk of anemia in relation to the duration of EBF and maternal anemia in a birth cohort studied between March 1998 and April 2003. All infant birth weights were >or=2.2 kg. All mothers received home-based peer counseling to promote EBF. Infant feeding data were collected weekly. Nurses measured hemoglobin (Hb) values every 3 mo. Hb was measured in 183 infants at 9 mo of age. Anemia at 9 mo was defined as a Hb value <100 g/L. EBF was defined by WHO criteria and ranged in duration from 0 to 31 wk. At 9 mo, Hb (mean +/- SEM) was 114 +/- 0.9 g/L; 23 children (12.5%) had Hb levels <100 g/L. EBF >6 mo, but not EBF 4-6 mo, was associated with increased risk of infant anemia compared with EBF <4 mo (odds ratio=18.4, 95% CI=1.9, 174.0). Maternal anemia was independently (P=0.03) associated with a 3-fold increased risk of infant anemia. These associations were not explained by confounding with other maternal or infant factors. By linear regression, a lower infant Hb at 9 mo was associated with increased EBF duration among mothers who had a history of anemia (beta=-0.07, P=0.003), but not among mothers with no history of anemia. Infants who are exclusively breast-fed for >6 mo in developing countries may be at increased risk of anemia, especially among mothers with a poor iron status; greater attention to this issue is warranted.

Anemia↗
PubMed2005

Human-milk glycans that inhibit pathogen binding protect breast-feeding infants against infectious diarrhea.

Breast-feeding is a highly effective strategy for preventing morbidity and mortality in infancy. The human-milk glycans, which include oligosaccharides in their free and conjugated forms, constitute a major and an innate immunologic mechanism by which human milk protects breast-fed infants against infections. The glycans found in human milk function as soluble receptors that inhibit pathogens from adhering to their target receptors on the mucosal surface of the host gastrointestinal tract. The alpha1,2-linked fucosylated glycans, which require the secretor gene for expression in human milk, are the dominant glycan structure found in the milk of secretor mothers, who constitute the majority ( approximately 80%) of mothers worldwide. In vitro and in vivo binding studies have demonstrated that alpha1,2-linked fucosylated glycans inhibit binding by campylobacter, stable toxin of enterotoxigenic Escherichia coli, and major strains of caliciviruses to their target host cell receptors. Consistent with these findings, recently published epidemiologic data demonstrate that higher relative concentrations of alpha1,2-linked fucosylated glycans in human milk are associated with protection of breast-fed infants against diarrhea caused by campylobacter, caliciviruses, and stable toxin of enterotoxigenic E. coli, and moderate-to-severe diarrhea of all causes. These novel data open the potential for translational research to develop the human-milk glycans as a new class of antimicrobial agents that prevent infection by acting as pathogen anti-adhesion agents.

Breast Feeding↗
PubMed2005

Human milk glycans protect infants against enteric pathogens.

Breastfed infants have lower morbidity and mortality due to diarrhea than those fed artificially. This had been attributed primarily to the secretory antibodies and prebiotic factors in human milk. Oligosaccharides are the third largest component of human milk. They were initially considered to be functionless by-products of glycoprotein and glycolipid synthesis during milk production. However, in the past few decades it has become apparent that the human milk oligosaccharides are composed of thousands of components, at least some of which protect against pathogens. Oligosaccharide protection against infectious agents may result in part from their prebiotic characteristics, but is thought to be primarily due to their inhibition of pathogen binding to host cell ligands. Most human milk oligosaccharides are fucosylated, and their production depends on enzymes encoded by the genes associated with expression of the Lewis blood group system. The expression of specific fucosylated oligosaccharides in milk thus varies in relation to maternal Lewis blood group type, and is significantly associated with the risk of infectious disease in breastfed infants. Specific fucosylated moieties of oligosaccharides and related glycoconjugates (glycans) are able to inhibit binding and disease by specific pathogens. This review presents the argument that specific glycans, especially the oligosaccharides, are the major constituent of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. The large input of energy expended by the mother in the synthesis of milk oligosaccharides is consistent with the human reproductive strategy of large parental input into rearing relatively few offspring through a prolonged period of maturation. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit diseases caused by mucosal pathogens.

Bacterial Infections↗
PubMed2004

Human milk contains elements that block binding of noroviruses to human histo-blood group antigens in saliva.

Noroviruses (NVs) recognize human histo-blood group antigens (HBGAs) as receptors. We characterized the interaction of human milk samples with recombinant virus-like particles representing VA387, Norwalk, VA207, and MOH. Milk samples from 60 healthy women were tested for human HBGAs and for their ability to block the binding of NVs. Fifty-four women were secretors (Se+), and 6 were nonsecretors (Se-). No women had detectable A or B antigens in their milk samples. All 54 Se+ milk samples, but 0 of 6 Se- milk samples, blocked VA387 and Norwalk virus (Se+ binders) from binding to saliva samples. All 6 Lewis-positive Se- milk samples blocked binding to VA207, and variable blocking activities were exhibited by the Se+ milk samples. No milk samples blocked the binding of MOH to A and B antigens. Secretor and Lewis, but not A or B antigens, were present in human milk and were responsible for blocking NV binding to receptors and therefore are likely to be decoy receptors that protect breast-fed infants from NV infection.

Blood Group Antigens↗
PubMed2004

Seroepidemiology and risk factors for sporadic norovirus/Mexico strain.

Risk factors associated with transmission of sporadic norovirus (NV; formerly Norwalk-like virus)/Mexico strain were identified in a seroepidemiological study conducted in rural Mexico. Acquisition of Mexico strain IgA antibodies was age-related; 34% of 1-4-year-olds were seropositive, compared with 81% of adults (P<.001). After 12 months, 42% of 1-4-year-olds showed a seroresponse to Mexico strain, compared with 27% of adults (P<.01). Personal and domestic hygiene measures, such as hand washing, general cleanliness of the mother's clothing, and the type of room assigned for cooking were significantly associated with odds of a seroresponse. For infants, having a dog in or near the home was a risk factor for seroresponse (P<.01), whereas, for older children, the mother's involvement in agricultural activities was a risk factor (P<.001). This study provides initial evidence of risk factors associated with sporadic NV infection. Data indicate some similarities to risk factors associated with outbreaks of NV infection.

Adolescent↗
PubMed2004

Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants.

OBJECTIVE: To determine the association between maternal milk levels of 2-linked fucosylated oligosaccharide and prevention of diarrhea as a result of Campylobacter, caliciviruses, and diarrhea of all causes in breast-fed infants. STUDY DESIGN: Data and banked samples were analyzed from 93 breast-feeding mother-infant pairs who were prospectively studied during 1988-1991 from birth to 2 years with infant feeding and diarrhea data collected weekly; diarrhea was diagnosed by a study physician. Milk samples obtained 1 to 5 weeks postpartum were analyzed for oligosaccharide content. Data were analyzed by Poisson regression. RESULTS: Total 2-linked fucosyloligosaccharide in maternal milk ranged from 0.8 to 20.8 mmol/L (50%-92% of milk oligosaccharide). Moderate-to-severe diarrhea of all causes (n=77 cases) occurred less often (P=.001) in infants whose milk contained high levels of total 2-linked fucosyloligosaccharide as a percent of milk oligosaccharide. Campylobacter diarrhea (n=31 cases) occurred less often (P=.004) in infants whose mother's milk contained high levels of 2'-FL, a specific 2-linked fucosyloligosaccharide, and calicivirus diarrhea (n=16 cases) occurred less often (P=.012) in infants whose mother's milk contained high levels of lacto-N-difucohexaose (LDFH-I), another 2-linked fucosyloligosaccharide. CONCLUSION: This study provides novel evidence suggesting that human milk oligosaccharides are clinically relevant to protection against infant diarrhea.

Adolescent↗
PubMed2004

A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis.

The need for safe and effective vaccines to reduce morbidity and mortality caused by rotavirus gastroenteritis in children is well-known. A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need. An overview of RIX4414 trials in developed and developing settings is presented for 3 selected trials conducted in Finland (pilot study), Latin America (Brazil, Mexico and Venezuela) and Singapore involving 5024 infants. The vaccine was well-tolerated, with no increase in any solicited symptoms as compared with the placebo. After 2 doses, 61-91% of vaccinated infants developed rotavirus-specific IgA antibodies. There was no interference with immunogenicity of coadministered routine pediatric vaccines. Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05). Vaccine efficacy was observed against severe rotavirus gastroenteritis caused by G1 and non-G1 types including the emerging G9 type (P < 0.05) in Latin America. These results show prospects for widespread use of Rotarix to reduce rotavirus disease burden and warrant continued worldwide evaluation.

Clinical Trials as Topic↗
PubMed2003

Innate protection conferred by fucosylated oligosaccharides of human milk against diarrhea in breastfed infants.

To test the hypothesis that human milk fucosyloligosaccharides are part of an innate immune system, we addressed whether their expression (1) depends on maternal genotype and (2) protects breastfed infants from pathogens. Thus the relationship between maternal Lewis blood group type and milk oligosaccharide expression and between variable oligosaccharide expression and risk of diarrhea in their infants was studied in a cohort of 93 Mexican breastfeeding mother-infant pairs. Milk of the 67 Le(a-b+) mothers contained more LNF-II (Le(a)) and 3-FL (Le(x)) (oligosaccharides whose fucose is exclusively alpha 1,3- or alpha 1,4-linked) than milk from the 24 Le(a-b-) mothers; milk from Le(a-b-) mothers contained more LNF-I (H-1) and 2'-FL (H-2), whose fucose is exclusively alpha 1,2-linked. The pattern of oligosaccharides varied among milk samples; in each milk sample, the pattern was summarized as a ratio of 2-linked to non-2-linked fucosyloligosaccharides. Milks with the highest ratios were produced primarily by Le(a-b-) mothers; those with the lowest ratios were produced exclusively by Le(a-b+) mothers (p<0.001). Thus maternal genetic polymorphisms expressed as Lewis blood group types are expressed in milk as varied fucosyloligosaccharide ratios. The four infants who developed diarrhea associated with stable toxin of Escherichia coli were consuming milk with lower ratios (4.4 +/- 0.8 [SE]) than the remaining infants (8.5 +/- 0.8; p<0.001). Furthermore, the 27 infants who developed moderate to severe diarrhea of any cause were consuming milk with lower ratios (6.1 +/- 0.9) than the 26 who remained healthy (10.5 +/- 1.9; p = 0.042). Thus, milk with higher 2-linked to non-2-linked fucosyloligosaccharide ratios affords greater protection against infant diarrhea. We conclude that specific oligosaccharides constitute a major element of an innate immune system of human milk.

Adult↗
PubMed2003

Campylobacter jejuni binds intestinal H(O) antigen (Fuc alpha 1, 2Gal beta 1, 4GlcNAc), and fucosyloligosaccharides of human milk inhibit its binding and infection.

The most common cause of infant mortality is diarrhea; the most common cause of bacterial diarrhea is Campylobacter jejuni, which is also the primary cause of motor neuron paralysis. The first step in campylobacter pathogenesis is adherence to intestinal mucosa. We found that such binding was inhibited in vitro by human milk and, with high avidity, by alpha1,2-fucosylated carbohydrate moieties containing the H(O) blood group epitope (Fuc alpha 1,2Gal beta 1,4GlcNAc em leader ). In studies on the mechanism of adherence, campylobacter, which normally does not bind to Chinese hamster ovary cells, bound avidly when the cells were transfected with a human alpha1,2-fucosyltransferase gene that caused overexpression of H-2 antigen; binding was specifically inhibited by H-2 ligands (lectins Ulex europaeus and Lotus tetragonolobus and H-2 monoclonal antibody), H-2 mimetics, and human milk oligosaccharides. Human milk oligosaccharides inhibited campylobacter colonization of mice in vivo and human intestinal mucosa ex vivo. Campylobacter colonization of nursing mouse pups was inhibited if their dams had been transfected with a human alpha1,2-fucosyltransferase gene that caused expression of H(O) antigen in milk. We conclude that campylobacter binding to intestinal H-2 antigen is essential for infection. Milk fucosyloligosaccharides and specific fucosyl alpha1,2-linked molecules inhibit this binding and may represent a novel class of antimicrobial agents.

ABO Blood-Group System↗