Bovine lactoferrin is effective to suppress Helicobacter pylori colonization in the human stomach: a randomized, double-blind, placebo-controlled study

Bovine lactoferrin (bLF) has antibacterial activity against Helicobacter pylori in vitro and is effective to suppress bacterial colonization in mice. The aim of our study was to evaluate the efficacy of orally administered bLF on H. pylori colonization in humans by a randomized, double-blind, placebo-controlled study. Fifty-nine healthy subjects positive for H. pylori infection were recruited. Subjects were randomized into two groups. The bLF group received bLF tablets at a dosage of 200 mg b.i.d. for a period of 12 weeks, and the control group received placebo tablets without bLF. The ¹³C-urea breath test (UBT) was performed before, during, and at the end of administration, and again 4 weeks after administration. Positive response was defined as more than 50% decrease of the UBT value at the end of administration. Positive response was observed in 10 of 31 bLF-treated subjects (32.3%) and 1 of 28 control subjects (3.6%), indicating that the rate of positive response in the bLF group was significantly higher than that in the control group (bLF vs. control, P < 0.01). These results suggested that bLF administration is effective to suppress H. pylori colonization.     

The Assessment of a Rapid Noninvasive Immunochromatographic Assay Test for Fecal Lactoferrin in Patients with Suspected Inflammation of the Ileal Pouch

Purpose

Pouchitis is a common complication after ileal pouch-anal anastomosis. Diagnosis is based on the Pouch Disease Activity Index, which comprises clinical symptoms, endoscopic appearance, and histologic confirmation. A Pouch Disease Activity Index ≥ 7 confirms pouchitis. Fecal lactoferrin is a marker of intestinal inflammation, which can aid in the diagnosis of pouchitis. The IBD EZ VUE? test is a simple, rapid, noninvasive test for fecal lactoferrin. Our goal was to study the sensitivity and specificity of this test in the diagnosis of pouchitis.

Methods

Consecutive patients with pouch dysfunction were recruited from October 2005 to July 2006. A fecal sample was collected before calculation of the Pouch Disease Activity Index. An IBD EZ VUE? test was performed on each fecal sample and the results correlated with the diagnosis of pouchitis to calculate sensitivity and specificity of the IBD EZ VUE? test.

Results

There were 32 patients (21 healthy and 11 inflammed pouches). The IBD EZ VUE? test was positive in 14 patients. It had a sensitivity of 100 percent and a specificity of 86 percent in diagnosing pouchitis. The positive predictive value was 76 percent. There were three false-positive results.

Conclusions

The IBD EZ VUE? test is a sensitive method that may remove the need for invasive pouch investigations and lead to greater confidence when antibiotic therapy is commenced. Further investigations may be reserved for those patients who have a positive lactoferrin test and fail to respond to antibiotic treatment.     

Update of fecal markers of inflammation in inflammatory bowel disease

The diagnosis, prognosis, and assessment of disease activity of inflammatory bowel disease (IBD) require investigating clinical, radiological, and histological criteria, as well as serum inflammatory markers. However, a range of fecal inflammatory markers now appears to have the potential to greatly assist in these processes. Calprotectin, a prominent neutrophil protein, was identified two decades ago as a potentially revolutionary marker for IBD. Following this discovery, numerous additional markers, including S100A12, lactoferrin, and M2-pyruvate kinase, have also been suggested as novel markers of IBD. In the present study, we provide an up-to-date review of fecal markers of IBD, and further, provide a novel analysis of each of these fecal markers in severe ulcerative colitis and compare their expression pattern in contrast to calprotectin.     

Ascitic fluid analysis for diagnosis and monitoring of spontaneous bacterial peritonitis

Polymorphonuclear （PMN） cell count in the ascitic fluid is essential for the diagnosis and management of spontaneous bacterial peritonitis （SBP）. To date, PMN cell count is routinely performed by traditional manual counting. However, this method is time-consuming, costly, and not always timely available. Therefore, considerable efforts have been made in recent years to develop an alternative test for a more rapid diagnosis and monitoring of SBP. The use of urinary reagent strips was proposed to achieve an ＂instant＂ bedside diagnosis of SBP. A series of reports evaluated the urine strip test for SBP diagnosis and reported promising results. However, a recent large multicenter study revealed a surprising lack of diagnostic efficacy of the urine screening test for SBP diagnosis. Another method, more recently proposed as an alternative to the manual PMN count, is the measurement of lactoferrin in ascitic fluid, but the data available on the diagnostic value of this test are limited to a single study. However, both urinary reagent strips and ascitic lactoferrin tests are qualitative methods and need, therefore, to be fur- ther confirmed by standard cytology of the ascitic fluid. To date, the only quantitative method proposed as a valid alternative to manual PMN counting is automated blood cell counters, commonly used in all laboratories for blood cell counting. Data available in the literature on the diagnostic performance of this method are limited but very promising, and this tool seems to have the potential to replace the manual counting method.     

Lactoferrin, C-reactive Protein, α-1-Antitrypsin and Immunoglobulin GA in Cerebrospinal Fluid in Meningitis

ABSTRACT. Cerebrospinal fluid measurements of lactoferrin and α-1-antitrypsin showed significant elevation in bacterial meningitis in children. 8 of 10 lactoferrin values and 6 of 11 α-1-antitrypsin values were above the upper range of controls. Both proteins correlated well with the total number of leukocytes in the cerebrospinal fluid. C-reactive protein, measured by either agglutination or radial immunodiffusion in the cerebrospinal fluid, failed to demonstrate any asefulness in diagnosing bacterial meningitis. Neither elevated serum C-reactive protein in cases of bacterial meningitis, nor sepsis, gave detectable concentrations of C-reactive protein in the cerebrospinal fluid.     

重组人乳铁蛋白对缺铁性贫血大鼠铁营养状况的改善作用

目的研究从转基因牛乳中分离纯化的重组人乳铁蛋白(rhLf)对缺铁性贫血(IDA)大鼠铁营养状况是否具有改善作用。方法雌性断乳Wistar大鼠喂饲低铁饲料建立IDA模型,按造模结束时Hb和体重随机分为6组,即模型对照组(A组),0.375、0.75和2.25g/kg BW rhLf组(B、C、D组),0.011g/kg BW乳酸亚铁组(E组),0.375g/kg BW rhLf与0.011g/kg BW乳酸亚铁联合补充组(F组),每组12只,每天一次性灌胃给予受试物,连续8周。检测指标包括动物一般情况、体重变化、Hb和RBC、游离原卟啉(FEP)、血清铁(SI)、总铁结合力(TIBC)、运铁蛋白饱和度(TS)、血清铁蛋白(SF)、血清Cu和血清Zn。结果与A组相比,E、F组大鼠一般情况明显改善,体重、RBC、Hb、SI、TS和SF显著增加,FEP、TIBC和血清Zn降低,机体铁营养状态基本恢复正常;D组上述指标较A组同样有显著性差异,但改善程度低于E、F组,动物仍处于缺铁状态;C组RBC较A组显著增加,FEP和血清Zn显著降低,其他指标无差异;B组仅血清Zn显著低于A组,其他指标无差异。E、F两组比较时,F组SI、TS和SF均显著高于E组,TIBC低于E组。结论单纯补充rhLf对IDA大鼠铁营养状况具有一定程度的改善作用,但较乳酸亚铁弱;乳酸亚铁与rhLf联合应用时改善机体铁营养状况的作用强于单纯补充乳酸亚铁或rhLf,同时可减轻亚铁离子导致的不良反应。     

Bovine lactoferrin digested with human gastrointestinal enzymes inhibits replication of human echovirus 5 in cell culture

Many infant formulas are enriched with lactoferrin (Lf) because of its claimed beneficial effects on health. Native bovine Lf (bLf) is known to inhibit in vitro replication of human enteroviruses, a group of pathogenic viruses that replicate in the gut as their primary infection site. On the basis of a model digestion and human gastrointestinal enzymes, we hypothesized that bLf could retain its antiviral properties against enterovirus in the gastrointestinal tract, either as an intact protein or through bioactive peptide fragments released by digestive enzymes. To test our hypothesis, bLf was digested with human gastric juice and duodenal juice in a 2-step in vitro digestion model. Two gastric pH levels and reduction conditions were used to simulate physiological conditions in adults and infants. The antiviral activity of native bLf and of the digested fractions was studied on echovirus 5 in vitro, using various assay conditions, addressing several mechanisms for replication inhibition. Both native and digested bLf fractions revealed a significant inhibitory effect, when added before or simultaneously with the virus onto the cells. Furthermore, a significant stronger sustained antiviral effect was observed when bLf was fully digested in the gastric phase with fast pH reduction to 2.5, compared with native bLf, suggesting the release of antiviral peptides from bLf during the human digestion process. In conclusion, this study demonstrates that bLf may have a role in the prevention of human gastrointestinal virus infection under physiological conditions and that food containing bLf may protect against infection in vivo.     

Lactoferrin and the newborn: current perspectives

Neonatal sepsis and necrotizing enterocolitis (NEC) are associated with significant mortality and morbidity. Inflammation secondary to sepsis and NEC increases morbidity, especially those related to the lung, brain and eye. Therapeutic strategies that target inflammation and decrease the emergence of antibiotic resistance are urgently needed. Lactoferrin (Lf) is a multifunctional protein that modulates inflammation, cell growth and differentiation and has broad antimicrobial activity. Studies evaluating the efficacy and safety of Lf in the prevention of neonatal sepsis and NEC are currently in progress, and one completed study shows significant promise. In this article, the functions of this multifunctional molecule and current clinical evidence for its use in the newborn are reviewed. Lf prophylaxis and therapy may have a significant impact in improving clinical outcomes of vulnerable preterm neonates.     

Faecal calprotectin and lactoferrin values during irradiation of prostate cancer correlate with chronic radiation proctitis: Results of a prospective study

Objective. Acute proctitis and chronic radiation proctitis are relevant complications of pelvic radiation. The purpose of this study was to investigate two markers of gut inflammation during and after irradiation for prostate cancer to evaluate a correlation between acute and chronic proctitis. Material and methods. Two patient groups were analysed. In group 1, stool samples from 20 patients were collected before therapy, every week during therapy, at the end of therapy, and 13 and 27 months after therapy. Group 2 comprised 47 patients who had undergone irradiation 40 months earlier. Toxicity was determined by common toxicity criteria (CTC) and the LENT soma scale. Calprotectin and lactoferrin values were determined by ELISA. Results. In group 1, acute values for both faecal markers were significantly correlated with chronic proctitis symptoms and all patients with chronic toxicity had acute proctitis symptoms with elevated faecal values. In group 2, where stool samples were solely collected 40 months after irradiation, the Pearson square test showed both a significant correlation between calprotectin and lactoferrin values and toxicity after 40 months. Conclusions. Within a group of 19 patients followed for two years after irradiation for prostate cancer, and 47 patients tested 40 months after irradiation, increased faecal values of calprotectin and lactoferrin were significantly correlated with the occurrence of chronic proctitis. This observation should be confirmed in an expanded study.     

Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.