What is the effect of lactoferrin on oral and jawbone tissue repair? A systematic review.

Currently, there is growing interest in the potential use of lactoferrin (LTF), a member of the transferrin family, for the improvement of tissue healing. In this sense, a literature search was conducted to integrate data published on the effect of LTF on jawbone repair. PubMed/MEDLINE, Scopus, Embase, Web of Science, LILACS, and Cochrane databases were retrieved according to the PRISMA 2020 statement. Articles in English, Spanish, and Portuguese were recovered, with no year restriction. In vitro, in vivo, and clinical studies were selected. A total of 742 articles were retrieved, 11 of which met the inclusion criteria (5 in vitro and 5 in vivo studies, and one clinical trial). The included data demonstrated wide variations in study design and LTF therapy protocols. Cell proliferation and viability were the primary outcomes evaluated in the in vitro studies, all of which reported a potential effect of LTF on the repair process. Of three in vivo studies, one reported a reduction in the overall healing rate, whereas the other two showed that LTF inhibited bone resorption and increased bone formation. The clinical trial's findings showed that LTF is a potential promoter of wound repair in patients with medication-related osteonecrosis of the jaws. Overall, data from the studies support a potential effect of LTF therapy on the process of jawbone repair.

Bovine lactoferrin for the prevention of COVID-19 infection in health care personnel: a double-blinded randomized clinical trial (LF-COVID).

Lactoferrin (LF) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to determine the effect of bovine lactoferrin (bLF) in the prevention of SARS-CoV-2 infection in health care personnel. A randomized, double-blinded, placebo-controlled clinical trial was conducted in two tertiary hospitals that provide care to patients with SARS-CoV-2 infection in Lima, Peru. Daily supplementation with 600 mg of enteral bLF versus placebo for 90 days was compared. Participants were weekly screened for symptoms suggestive of SARS-CoV-2 infection and molecular testing was performed on suspected episodes. A serological test was obtained from all participants at the end of the intervention. The main outcome included symptomatic and asymptomatic cases. A sub-analysis explored the time to symptomatic infection. Secondary outcomes were the severity, frequency, and duration of symptomatic infection. The study was prematurely cancelled due to the availability of vaccines against SARS-CoV-2 in Peru. 209 participants were enrolled and randomized, 104 received bLF and 105 placebo. SARS-CoV-2 infection occurred in 11 (10.6%) participants assigned to bLF and in 9 (8.6%) participants assigned to placebo without significant differences (Incidence Rate Ratio = 1.23, 95%CI 0.51-3.06, p-value = 0.64). There was no significant effect of bLF on time to symptomatic infection (Hazard Ratio = 1.61, 95%CI 0.62-4.19, p-value = 0.3). There were no significant differences in secondary outcomes. A significant effect of bLF in preventing SARS-CoV-2 infection was not proven. Further studies are needed to assess the effect of bLF supplementation on SARS-CoV-2 infection.Clinical trial registration ClinicalTrials.gov Identifier: NCT04526821, https://clinicaltrials.gov/ct2/show/NCT04526821?term=LACTOFERRIN&cond=COVID-19&cntry=PE&city=Lima&draw=2&rank=1 .

Lactoferrin: An Effective Weapon in the Battle Against Bacterial Infections.

The emergence of multidrug-resistant bacterial strains with respect to commercially available antimicrobial drugs has marked a watershed in treatment therapies to fight pathogens and has stimulated research on alternative remedies. Proteins of the innate immune system of mammals have been highlighted as potentially yielding possible treatment options for infections. Lactoferrin (Lf) is one of these proteins; interestingly, no resistance to it has been found. Lf is a conserved cationic nonheme glycoprotein that is abundant in milk and is also present in low quantities in mucosal secretions. Moreover, Lf is produced and secreted by the secondary granules of neutrophils at infection sites. Lf is a molecule of approximately 80 kDa that displays multiple functions, such as antimicrobial, anti-viral, anti-inflammatory, and anticancer actions. Lf can synergize with antibiotics, increasing its potency against bacteria. Lactoferricins (Lfcins) are peptides resulting from the N-terminal end of Lf by proteolytic cleavage with pepsin. They exhibit several anti-bacterial effects similar to those of the parental glycoprotein. Synthetic analog peptides exhibiting potent antimicrobial properties have been designed. The aim of this review is to update understanding of the structure and effects of Lf and Lfcins as anti-bacterial compounds, focusing on the mechanisms of action in bacteria and the use of Lf in treatment of infections in patients, including those studies where no significant differences were found. Lf could be an excellent option for prevention and treatment of bacterial diseases, mainly in combined therapies with antibiotics or other antimicrobials.

Randomized Controlled Trial of Bovine Lactoferrin for Prevention of Sepsis and Neurodevelopment Impairment in Infants Weighing Less Than 2000 Grams.

OBJECTIVES: To determine the effect of bovine lactoferrin on prevention of late-onset sepsis (LOS) and neurodevelopment delay. STUDY DESIGN: Randomized, double-blind, controlled trial in neonates with a birth weight of 500-2000 g in 3 neonatal units in Lima, Peru, comparing bovine lactoferrin 200 mg/kg/day with placebo administered for 8 weeks. The primary outcome was the first episode of culture-proven LOS or sepsis-associated death. Neurodevelopment delay was assessed by the Mullen Scales at 24 months corrected age. RESULTS: Of the 414 infants enrolled, 209 received bovine lactoferrin and 205 received placebo. LOS or sepsis-associated death occurred in 22 infants (10.5%) in the bovine lactoferrin group vs 30 (14.6%) in the placebo group; there was no difference after adjusting for hospital and birth weight; hazard ratio 0.73 (95% CI, 0.42-1.26). For infants with birth weights of <1500 g the hazard ratio was 0.69 (95% CI, 0.39-1.25). The mean age-adjusted normalized Mullen composite score at 24 months was 83.3 ± 13.6 in the bovine lactoferrin group vs 82.6 ± 13.1 in the placebo group. Growth outcomes and rehospitalization rates during the 2-year follow-up were similar in both groups, except for significantly less bronchiolitis in the bovine lactoferrin group (rate ratio, 0.34; 95% CI, 0.14-0.86). CONCLUSIONS: Supplementation with bovine lactoferrin did not decrease the incidence of sepsis in infants with birth weights of <2000 g. Growth and neurodevelopment outcomes at 24 months of age were similar. Neonatal bovine lactoferrin supplementation had no adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01525316.

Cytokine responses to symbiotic and lactoferrin combination in very low birth weight neonates: a randomized control trial. / Respuesta de las citocinas a la combinación de simbióticos y lactoferrina en recién nacidos de muy bajo peso al nacer: ensayo controlado aleatorizado.

INTRODUCTION: Probiotics and prebiotics, which are multifunctional agents, have potential benefits in chronic mucosal inflammation, including the prevention of necrotizing enterocolitis. However, the mechanisms and the results of these immunomodulatory effects are not clear. This study aimed to investigate the cytokine response to the combination of Lactobacillus and Bifidobacterium together with fructo- and galacto-oligosaccharides (symbiotic) and lactoferrin in very low birth weight neonates. POPULATION AND METHODS: Infants ≤ 32 GWs and ≤ 1,500 g were randomly assigned to receive a symbiotic combination or 1 ml distilled water as placebo starting with the first feed until discharge. Blood samples were obtained at postnatal 0 ± 2, 14 ± 2, and 28 ± 2 days, and the serum levels of interferon-y, interleukin (IL)-5, IL-10, and IL-17A were measured. RESULTS: In the study group (n = 25), the IL-10 levels decreased throughout the study period (p = 0.011) but did not change in the control group. The IL-5 levels remained steady in the first 14 days and decreased significantly thereafter (p = 0.042) in the study group, whereas they increased in the first 14 days (p = 0.019), and then decreased in 28 days (p = 0.011) in the control group (n = 25). The levels of the other cytokines did not change throughout the study period. CONCLUSION: The combined use of probiotics with oligosaccharides and lactoferrin was associated with a decrease in IL-10 levels, but no change was observed in the other cytokines.

Introducción: Los probióticos y prebióticos presentan beneficios potenciales en la inflamación crónica de las mucosas, incluida la prevención de la enterocolitis necrosante. No obstante, los mecanismos y resultados de estos efectos inmunomoduladores son confusos. El objetivo fue investigar la respuesta de las citocinas a Lactobacillus y Bifidobacterium asociados con fructo- y galactooligosacáridos (simbióticos) y lactoferrina en recién nacidos de muy bajo peso al nacer. Población y métodos: Se asignó aleatoriamente a lactantes con ≤32 semanas de gestación y ≤1500 g de peso para recibir simbióticos o 1 ml de agua destilada como placebo desde la primera alimentación hasta el alta. Se obtuvieron muestras de sangre los días posnatales 0 ± 2, 14 ± 2 y 28 ± 2, y se midieron interferón-y, interleucina (IL)-5, IL-10 e IL-17A. Resultados: En el grupo del estudio (n = 25), la concentración de IL-10 disminuyó a lo largo del estudio (p = 0,011), pero no cambió en el grupo de referencia. La concentración de IL-5 se mantuvo constante los primeros 14 días y luego disminuyó significativamente (p = 0,042) en el grupo del estudio, mientras que aumentó en los primeros 14 días (p = 0,019) y luego disminuyó en 28 días (p = 0,011) en el grupo de referencia (n = 25).La concentración de otras citocinas no cambió a lo largo del estudio. Conclusión: El uso combinado de probióticos con oligosacáridos y lactoferrina estuvo asociado con una disminución en la concentración de IL-10, pero no se observó un cambio en las otras citocinas.

Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants.

OBJECTIVE: To evaluate the safety and explore the efficacy of recombinant human lactoferrin (talactoferrin [TLf]) to reduce infection. STUDY DESIGN: We conducted a randomized, double blind, placebo-controlled trial in infants with birth weight of 750-1500 g. Infants received enteral TLf (n = 60) or placebo (n = 60) on days 1 through 28 of life; the TLf dose was 150 mg/kg every 12 hours. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis, and necrotizing enterocolitis (NEC). Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory, and radiologic findings, along with diseases and adverse events, in a database used for statistical analyses. RESULTS: Demographic data were similar in the 2 groups of infants. We attributed no enteral or organ-specific adverse events to TLf. There were 2 deaths in the TLf group (1 each due to posterior fossa hemorrhage and postdischarge sudden infant death), and 1 death in the placebo group, due to NEC. The rate of hospital-acquired infections was 50% lower in the TLf group compared with the placebo group (P < .04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants in the TLf group weighing <1 kg at birth had no gram-negative infections, compared with only 3 of 14 such infants in the placebo group. Noninfectious outcomes were not statistically significantly different between the 2 groups, and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period. CONCLUSION: We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00854633.

Randomized Control Trial of Human Recombinant Lactoferrin: A Substudy Reveals Effects on the Fecal Microbiome of Very Low Birth Weight Infants.

UNLABELLED: The purpose of this study is to evaluate the effects of enteral lactoferrin on the fecal microbiome and contrast those influences with the neonatal intensive care unit (NICU) environment. We theorized that lactoferrin and the NICU habitat shape the fecal microbial composition of very preterm infants. Although functions attributed to lactoferrin include intestinal immune system development and emergence of a healthy gut microbiota, evidence is limited. Twenty-one very low birth weight (VLBW <1500 g) infants received twice-daily talactoferrin (TLf, a drug designation for recombinant human lactoferrin) or its excipient by gastric gavage from day 1-28 of life. Twenty-four-hour fecal samples were collected on day 21 of life and compared with fecal operational taxonomy units (OTUs) in treated and control infants in 2 NICUs. Workflow included fecal DNA isolation, generation of amplicons for the V1-V3 region of bacterial 16S ribosomal RNA, and sequencing of a gel-purified multiplex amplicon library using a Roche 454 GS FLX Titanium (Roche, Branford, Connecticut) platform and protocols. Fecal OTUs per infant were higher in NICU 1 vs NICU 2 (P < .001), consistent with fewer antibiotic days (P < .02) and a shorter duration of parenteral nutrition (P < .007) in NICU 1. Proteobacteria and Firmicutes were the major phyla in infants treated with TLf and placebo. Among Enterobacteriaceae, TLf prophylaxis reduced Enterobacter and Klebsiella, but increased Citrobacter in feces of VLBW infants. Citrobacter caused no neonatal infections in the study population. OTUs for Clostridiaceae increased in NICU 1 among infants treated with TLf. Importantly, OTUs of staphylococci were barely detectable in both NICUs among infants fed TLf. Fewer hospital-acquired infections occurred in infants treated with TLf vs controls, although the reduction was seen mostly in coagulase-negative staphylococci-related bloodstream and central line infections (P = .06). TLf modified the fecal microbiome in VLBW infants, but care practices in the NICU habitat also contributed. Future research must establish whether elimination vs enrichment of gut-related microbiota reduces clinically significant hospital-acquired infections and promotes a healthy commensal microflora in the intestines of VLBW infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00854633.

Clinical Benefits of Lactoferrin for Infants and Children.

To discuss the potential clinical benefits of lactoferrin in preterm and term infants, as well as in young children and to review information on the burden of neonatal sepsis. Current evidence on the mechanisms that explain the role of human milk in the neonatal and infant anti-infective responses will be briefly reviewed and preclinical research data on the potential mechanisms of action by which lactoferrin may impact infant gut health, gut immune development and functions, including the lactoferrin effects on the neonatal microbiome, will be examined. Finally, updated translational research on lactoferrin will be presented and discussed and the current evidence from prospective randomized controlled trials in neonates, infants, and toddlers will be analyzed. These randomized controlled trials demonstrate that lactoferrin has a clinically significant impact on feeding, the microbiome, and clinical outcomes in neonates and infants.

Rotavirus seasonal distribution and prevalence before and after the introduction of rotavirus vaccine in a peri-urban community of Lima, Peru.

We evaluated the monthly distribution of rotavirus diarrhea in a cohort of children 12-24 months of age followed as part of a diarrhea clinical trial in a peri-urban community of Lima. We observed a peak of rotavirus diarrhea in the winter months and a decrease in rotavirus prevalence after the introduction of the rotavirus vaccine in Peru.

Lactoferrin for prevention of neonatal sepsis.

Preterm neonates are at risk to acquire infections. In addition to the high mortality associated with sepsis, these patients are at risk for long-term disabilities, particularly neurodevelopment impairment. Several interventions have been evaluated to reduce rates of infections in neonates but have not proven efficacy. Lactoferrin (LF), a milk glycoprotein with anti-inflammatory, immunomodulatory and anti-microbial properties, has the potential to prevent infections in young children. We performed a review of current and ongoing clinical trials of LF for prevention of neonatal sepsis, and found eleven registered clinical trials that include more than 6,000 subjects. Few of these trials have finished; despite their small sample size, the preliminary results show a trend towards a positive protective effect of LF on neonatal infections. Larger trials are underway to confirm the findings of these initial studies. This information will help to define LF's role in clinical settings and, if proven effective, would profoundly affect the treatment of low birth weight neonates as a cost-effective intervention worldwide.

Protective effect of human lactoferrin in the gastrointestinal tract.

OBJECTIVE: To describe mechanisms of action of human lactoferrin to protect gastrointestinal morbidities. DATA SOURCES: Nonsystematic literature review using the following databases: SciELO, Lilacs and Medline from 1990 to 2011. The key-words used were lactoferrin, human milk/breastfeeding, gastrointestinal, and immunity, in Portuguese and English. DATA SYNTHESIS: Lactoferrin is the second predominant protein in the human milk, with higher concentrations in the colostrum (5.0 to 6.7mg/mL) if compared to mature milk (0.2 to 2.6mg/mL.) In contrast, cow's milk has lower levels, with 0.83mg/mL in the colostrum and 0.09mg/mL in the mature milk. Lactoferrin has several physiological functions to protect the gastrointestinal tract. The antimicrobial activity is related to the ability to sequester iron from biological fluids and/or to destruct the membrane of microorganisms. Lactoferrin also has the ability to stimulate cell proliferation. The anti-inflammatory action exercised by lactoferrin is associated with its ability to penetrate the core of the leukocyte and to block the Kappa B nuclear factor transcription. Given the importance of lactoferrin to prevent infectious diseases for breastfed children, the industry is using genetic engineering techniques to develop the expression of recombinant human lactoferrin in animals and plants, attempting to adjust the composition of infant formulas to that of human milk. CONCLUSIONS: Human lactoferrin is a peptide with great potential for preventing morbidity, especially in the gastrointestinal tract. Scientific evidence of the protective effects of human lactoferrin strengthens even more the recommendation for breastfeeding.

Efeito protetor da lactoferrina humana no trato gastrintestinal / Protective effect of human lactoferrin in the gastrointestinal tract / Efecto protector de la lactoferrina humana en el sistema gastrointestinal

OBJETIVO: Descrever os mecanismos de ação da lactoferrina humana na proteção de morbidades gastrintestinais. FONTES DE DADOS: Revisão não sistemática da literatura utilizando como estratégia de busca pesquisa bibliográfica em bases de dados, as quais incluíram SciELO, Lilacs e MedLine entre 1990 e 2011. Os descritores utilizados foram: lactoferrina, leite materno/humano, gastrintestinal e imunidade, nos idiomas português e inglês. SÍNTESE DOS DADOS: A lactoferrina é a segunda proteína predominante no leite humano, com concentrações mais elevadas no colostro (5,0 a 6,7mg/mL) em relação ao leite maduro (0,2 a 2,6mg/mL). Em contraste, o leite de vaca contém teores inferiores, 0,83mg/mL no colostro e 0,09mg/mL no leite maduro. A lactoferrina desempenha diversas funções fisiológicas na proteção do trato gastrintestinal. A atividade antimicrobiana está relacionada à capacidade de sequestrar ferro dos fluidos biológicos e/ou de desestruturar a membrana de micro-organismos. A lactoferrina possui também a capacidade de estimular a proliferação celular. A ação anti-inflamatória desempenhada pela lactoferrina está associada à capacidade de penetrar no núcleo do leucócito e bloquear a transcrição do fator nuclear Kappa B. Diante da importância da lactoferrina na prevenção de doenças infecciosas em crianças aleitadas ao peito, a indústria vem, por meio da engenharia genética, desenvolvendo tecnologias para expressar esta proteína recombinante humana em plantas e animais, na tentativa de adequar a composição das fórmulas infantis àquela do leite humano. CONCLUSÕES: A lactoferrina humana é um peptídeo com potencial para prevenir morbidades, especialmente às gastrintestinais. Evidências científicas dos efeitos protetores da lactoferrina humana fortalecem ainda mais a recomendação para prática do aleitamento materno.

OBJECTIVE: To describe mechanisms of action of human lactoferrin to protect gastrointestinal morbidities. DATA SOURCES: Nonsystematic literature review using the following databases: SciELO, Lilacs and Medline from 1990 to 2011. The key-words used were lactoferrin, human milk/breastfeeding, gastrointestinal, and immunity, in Portuguese and English. DATA SYNTHESIS: Lactoferrin is the second predominant protein in the human milk, with higher concentrations in the colostrum (5.0 to 6.7mg/mL) if compared to mature milk (0.2 to 2.6mg/mL.) In contrast, cow's milk has lower levels, with 0.83mg/mL in the colostrum and 0.09mg/mL in the mature milk. Lactoferrin has several physiological functions to protect the gastrointestinal tract. The antimicrobial activity is related to the ability to sequester iron from biological fluids and/or to destruct the membrane of microorganisms. Lactoferrin also has the ability to stimulate cell proliferation. The anti-inflammatory action exercised by lactoferrin is associated with its ability to penetrate the core of the leukocyte and to block the Kappa B nuclear factor transcription. Given the importance of lactoferrin to prevent infectious diseases for breastfed children, the industry is using genetic engineering techniques to develop the expression of recombinant human lactoferrin in animals and plants, attempting to adjust the composition of infant formulas to that of human milk. CONCLUSIONS: Human lactoferrin is a peptide with great potential for preventing morbidity, especially in the gastrointestinal tract. Scientific evidence of the protective effects of human lactoferrin strengthens even more the recommendation for breastfeeding.

OBJETIVO: Describir los mecanismos de acción de la lactoferrina humana en la protección de morbilidades gastrointestinales. FUENTES DE DATOS: Revisión no sistemática de la literatura utilizando como estrategia de búsqueda investigación bibliográfica en bases de datos, que incluyeron SciELO, Lilacs y MedLine entre 1990 y 2011. Los descriptores utilizados fueron: lactoferrina, leche materna/humana, gastrointestinal e inmunidad, en los idiomas portugués e inglés. SÍNTESIS DE LOS DATOS: La lactoferrina es la segunda proteína predominante en la leche humana, con concentraciones más elevadas en el calostro (5,0 a 6,7mg/mL) respecto a la leche madura (0,2 a 2,6mg/mL). En contraste, la leche de vaca contiene tenores inferiores, 0,83mg/mL en el calostro y 0,09mg/mL en la leche madura. La lactoferrina desempeña diversas funciones fisiológicas en la protección del sistema gastrointestinal. La actividad antimicrobiana está relacionada a la capacidad de secuestrar hierro de los fluidos biológicos y/o de desestructurar la membrana de microorganismos. La lactoferrina posee además la capacidad de estimular la proliferación celular. La acción antiinflamatoria desempeñada por la lactoferrina está asociada a la capacidad de penetrar en el núcleo del leucocito y bloquear la transcripción del nuclear factor Kappa B. Frente a la importancia de la lactoferrina en la prevención de enfermedades infecciosas en niños amamantados al pecho, la industria viene, por medio de ingeniería genética, desarrollando tecnologías para expresar esta proteína recombinante humana en plantas y animales en el intento de adecuar la composición de las fórmulas infantiles a aquella de la leche humana. CONCLUSIONES: La lactoferrina humana es un péptido con potencial para prevenir morbilidades, especialmente las gastrointestinales. Evidencias científicas de los efectos protectores de la lactoferrina humana fortalecen todavía más la recomendación para la práctica de la lactancia materna.

Randomized double-blind controlled trial of bovine lactoferrin for prevention of diarrhea in children.

OBJECTIVE: To determine the effect of bovine lactoferrin (bLF) on prevention of diarrhea in children. STUDY DESIGN: We conducted a community-based randomized double-blind placebo controlled trial comparing supplementation with bLF vs placebo. Previously weaned children were enrolled at 12-18 months and followed for 6 months with daily home visits for data collection and supplement administration. Anthropometric measures were done monthly. RESULTS: Five hundred fifty-five children were randomized: 277 to bLF and 278 to placebo; 65 dropped out; 147 894 doses were administered (92% compliance). Overall there were 91 446 child-days of observation and 1235 diarrhea episodes lasting 6219 days. The main pathogens isolated during diarrheal episodes were norovirus (35.0%), enteropathogenic E coli (11.4%), Campylobacter (10.6%), enteroaggregative E coli (8.4%), enterotoxigenic E coli (6.9%), and Shigella (6.6%). The diarrhea incidence was not different between groups: 5.4 vs 5.2 episodes/child/year for bLF and placebo, respectively (P = .375). However, the diarrhea longitudinal prevalence was lower in the bLF group vs placebo (6.6% vs 7.0%, P = .017), as well as the median duration of episodes (4.8 vs 5.3 days, P = .046), proportion of episodes with moderate or severe dehydration (1.0% vs 2.6%, P = .045), and liquid stools load (95.0 vs 98.6) liquid stools/child/year, P < .001). There were no adverse events related to the intervention. CONCLUSIONS: Although there was no decrease in diarrhea incidence, longitudinal prevalence and severity were decreased with LF.

Lactoferrin: structure, function and applications.

Lactoferrin (LF) is an 80 kDa iron-binding glycoprotein of the transferrin family that is expressed in most biological fluids and is a major component of the mammalian innate immune system. Its protective effects range from direct antimicrobial activities against a large panel of microorganisms, including bacteria, viruses, fungi and parasites, to anti-inflammatory and anticancer activities. These extensive activities are made possible by mechanisms of action utilising not only the capacity of LF to bind iron but also interactions of LF with molecular and cellular components of both host and pathogens. This review summarises the putative antimicrobial mechanisms, clinical applications and heterologous expression models for LF.

Effect of lactoferrin on enteric pathogens.

Much has been learned in recent years about the mechanisms by which breastfeeding improves child health and survival. However, there has been little progress in using these insights to improve pediatric care. Factors that are important for protecting the breast fed infant might be expected to decrease the adverse effects of weaning on diarrhea, growth, and development. Lactoferrin, an iron-binding protein with multiple physiological functions (anti-microbial, anti-inflammatory, and immunomodulatory), is one of the most important proteins present in mammalian milk. Protection against gastroenteritis is the most likely biologically relevant activity of lactoferrin. Multiple in vitro and animal studies have shown a protective effect of lactoferrin on infections with enteric microorganisms, including rotavirus, Giardia, Shigella, Salmonella and the diarrheagenic Escherichia coli. Lactoferrin has two major effects on enteric pathogens: it inhibits growth and it impairs function of surface expressed virulence factors thereby decreasing their ability to adhere or to invade mammalian cells. Thus, lactoferrin may protect infants from gastrointestinal infection by preventing the attachment by enteropathogens in the gut. Recently several clinical trials in children have started to address this issue. Whether lactoferrin can prevent a significant portion of diarrheal disease remains to be determined.

[Antimicrobial mechanisms and potential clinical application of lactoferrin]. / Actividad antimicrobiana de la lactoferrina: mecanismos y aplicaciones clínicas potenciales.

Lactoferrin (Lf) is an iron binding multifunctional glycoprotein that is present in several mucosal secretions like milk, tears and saliva. Lf is also an abundant component of the specific granules of neutrophils and can be released into the serum upon neutrophil degranulation. One of the functions of this protein is the transport of metals, but it is also an important component of the non-specific immune system. Human and bovine Lfs display a broad antimicrobial spectrum against Gram positive and Gram negative bacteria, fungi and several viruses. While the iron-binding properties were originally believed to be solely responsible for the host defense properties ascribed to lactoferrin, it is now known that other mechanisms contribute to the antimicrobial role of this glycoprotein. This review gives an overview of the knowledge of these mechanisms and the potential clinical applications of Lf against infections

Uso combinado del método cualitativo y del metanálisis en el enfoque diagnóstico de la diarrea infecciosa / Combined use of qualitative method and metanalysis on the diagnostic approach of infectious diarrhea

Objetivo: comparar la utilidad diagnóstica de pruebas índice en la identificación de la diarrea invasiva. Métodos: combinación de análisis cualitativo y cuantitativo (metanálisis). Identificación de datos y selección de los estudios: de 2603 referencias identificadas vía MEDLINE (1970-1994), listas de referencias y por correspondencia con expertos en el campo, 81 cumplieron los requerimientos de selección preestablecidos. De éstas, 25 contenían datos suficientes para un metanálisis adicional. Extracción de datos: en la revisión cualitativa, un autor extrajo información amplia sobre la utilidad diagnóstica de las pruebas índice y sobre las características metodológicas de los estudios. En el metanálisis, todos los datos de los artículos seleccionados fueron extraídos por un investigador, en tanto otro verificó su exactitud. Se calculó la tasa de verdaderos positivos (TPR) y de falsos positivos (FPR), a partir de cada tabla de contigencia de 2 por 2. Utilizando el método de transformación logística y regresión lineal ponderada de cuadros mínimos, se elaboró curvas resumen de las características operativas del receptor (SROC), para determinar la utilidad diagnóstica comparativa de las pruebas. Resultados del análisis de datos: el enfoque cualitativo no restrictivo identificó problemas metodológicos que fueron evaluados adicionalmente en el estudio cuantitativo. En el metanálisis, la graficación de TPR contra FPR, como curvas SROC, demostró puntos dispersos, indicando heterogeneidad. La curva de lactoferrina fecal mostró el mayor rendimiento y la de leucocitos fecales el menor rendimiento. Conclusiones: la lactoferrina fecal es la prueba con mayor utilidad diagnóstica en la identificación de la diarrea invasiva. Se propone la utilización del enfoque combinado cualitativo y metanalítico como un método adecuado de evaluación de utilidad de pruebas diagnósticas, tanto en la práctica clínica como en el proceso general de análisis de decisiones.

A prevenção primária-primária da cárie: evitar a infecção bacteriana / Primary-primary prevention of caries: to avoid the bacterial infection

A cárie dentária é considerada como uma doença multifatorial na qual a infecção com estreptococos mutans tem grande influência. A interação entre o microrganismo e o hospedeiro na fase inicial da cárie não causa um grande prejuizo, mas com o tempo causa danos irreversíveis ao hospedeiro. Um dos maiores desafios na prevenção da cárie hoje em dia é impedir a adesão de estreptococos mutans aos dentes na fase de erupção dentária. Quanto mais tarde a criança vier ser infeccionada com essas bactérias, menos cárie se desenvolverá. Além disso, como a erupção dos dentes é lenta e acontece em períodos, a colonização e distribuição das bactérias são determinadas por aquelas que já conseguiram estabelecer-se na boca durante a dentição primária. O controle da infecção é a chave de uma prevenção duradoura. Logo, se a microbiota estabelecida, não contiver estreptococos mutans será mínima a possibilidade de mudança de tal situação. Denominamos este quadro de prevenção-primária-primária. O presente artigo trata de vários métodos para alcançar esse objetivo: chupetas que liberam agentes preventivos durante a noite, o fortalecimento do sistema imune, a imunização passiva e ativa. Além disso é discutido o impacto para a saúde bucal no Brasil

Olho seco / Dry eye

Os principais aspectos do ôlho seco säo descritos bem como o quadro clínico. O tratamento através de lágrimas artificiais é pouco adequado e o futuro do tratamento está em inserts que liberem quantidades adequadas de umidade, associada a lisozima, lactoferrina, vitamina A e sem preservativos