lactoferrin and Leukopenia

To compare subcutaneously given molgramostim (GM-CSF) and sucralfate mouth washings to sucralfate mouth washings in prevention of radiation-induced mucositis.. Forty head and neck cancer patients were randomly assigned to use either GM-CSF and sucralfate (n = 20) or sucralfate alone (n = 20) during radiotherapy. Sucralfate was used as 1.0 g mouth washing 6 times daily after the first 10 Gy of radiotherapy, and 150-300 microg GM-CSF was given subcutaneously. The grade of radiation mucositis and blood cell counts were monitored weekly. Salivary lactoferrin was measured as a surrogate marker for oral mucositis.. We found no significant difference between the molgramostim and the control groups in the oral mucositis grade, oral pain, use of analgesic drugs, weight loss, or survival. The median maximum neutrophil counts (median, 9.2 x 10(9)/L vs. 5.9 x 10(9)/L, p = 0.0005), eosinophil counts (median, 1.3 x 10(9)/L vs. 0.2 x 10(9)/L, p = 0.0004), and salivary lactoferrin concentrations were higher in patients who received GM-CSF. The most common toxicities in the GM-CSF plus sucralfate group were skin reactions at the GM-CSF injection site (65%), fever (30%), bone pain (25%), and nausea (15%), whereas the toxicity of sucralfate given alone was minimal.. We found no evidence indicating that subcutaneously given GM-CSF reduces the severity of radiation-induced mucositis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Antifungal Agents; Biomarkers; Dose Fractionation, Radiation; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Injections, Subcutaneous; Lactoferrin; Leukopenia; Male; Middle Aged; Pain Measurement; Patient Selection; Prospective Studies; Radiation Injuries; Radiation-Protective Agents; Saliva; Stomatitis; Sucralfate

The aim of this study was to investigate whether technetium-99m labelled fluconazole can distinguish fungal from bacterial infections. Fluconazole was labelled with (99m)Tc and radiochemical analysis showed less than 5% impurities. The labelling solution was injected into animals with experimental infections. For comparison, we used two peptides for infection detection, i.e. UBI 29-41 and hLF 1-11, and human IgG, all labelled with (99m)Tc. Mice were infected with Candida albicans or injected with heat-killed C. albicans or lipopolysaccharides to induce sterile inflammation. Also, mice were infected with Staphylococcus aureus or Klebsiella pneumoniae. Next, accumulation of (99m)Tc-fluconazole and (99m)Tc-labelled peptides/IgG at affected sites was determined scintigraphically. (99m)Tc-fluconazole detected C. albicans infections (T/NT ratio=3.6+/-0.47) without visualising bacterial infections (T/NT ratio=1.3+/-0.04) or sterile inflammatory processes (heat-killed C. albicans: T/NT ratio=1.3+/-0.2; lipopolysaccharide: T/NT ratio=1.4+/-0.1). C. albicans infections were already seen within the first hour after injection of (99m)Tc-fluconazole (T/NT ratio=3.1+/-0.2). A good correlation (R(2)=0.864; P<0.05) between T/NT ratios for this tracer and the number of viable C. albicans was found. Although (99m)Tc-UBI 29-41 and (99m)Tc-hLF 1-11 were able to distinguish C. albicans infections from sterile inflammatory processes in mice, these (99m)Tc-labelled peptides did not distinguish these fungal infections from bacterial infections. It is concluded that (99m)Tc-fluconazole distinguishes infections with C. albicans from bacterial infections and sterile inflammations.

Topics: Animals; Aspergillosis; Aspergillus fumigatus; Candidiasis; Diagnosis, Differential; Fluconazole; Humans; Immunoglobulin G; Inflammation; Lactoferrin; Leukopenia; Lipopolysaccharides; Male; Mice; Myositis; Peptide Fragments; Radionuclide Imaging; Reproducibility of Results; Ribosomal Proteins; Sensitivity and Specificity; Technetium; Thigh; Tissue Distribution

Bovine lactoferrin was applied topically to the oral mucosa of Syrian hamsters and assessed for its ability to decrease the severity of chemotherapy-induced oral mucositis. Results indicated that the chemotherapy agent 5-fluorouracil (5-FU) administered to hamsters on days 0 and 2 produced severe leukopenia between days 4 and 7 of the trial, and that severity of oral mucositis coincided with the suppressed immune state in these animals. Bovine lactoferrin applied continuously to oral wounds in hamsters induced by a combination of chemotherapy treatment and mild abrasion of the cheek pouch, failed to decrease the severity of mouth ulcers relative to a group receiving BSA as a control protein source. Hamster cheek pouches treated twice daily with lactoferrin had a significantly worse condition score between days 6 and 8, and days 12 and 13 (p < 0.05 to p < 0.001), a higher ulcer score between days 6 and 15 (p < 0.05 to p < 0.001) and larger ulcer area between days 7 and 14 (p < 0.05 to p < 0.001) compared to animals administered the control protein. Body weight changes between treatment and control groups showed no significant difference over the trial period. In contrast to the pre-study hypothesis, we report a detrimental effect from topical administration of bovine lactoferrin to the wounded oral mucosa of immunocompromised hamsters.

Topics: Animals; Antimetabolites, Antineoplastic; Cheek; Cricetinae; Drug Evaluation; Fluorouracil; Immunocompromised Host; Lactoferrin; Leukopenia; Mesocricetus; Mouth Mucosa; Stomatitis; Wound Healing

Topics: Adult; Cytokines; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Lactoferrin; Leukopenia; Middle Aged; Secretory Rate; Transplantation Conditioning; Transplantation, Autologous

Removal of beta 2-microglobulin has become a major objective of dialysis therapy. The present study was performed to evaluate both compatibility and elimination capacity for beta 2-microglobulin of a newly developed high-flux polyamide membrane (Polyflux 130) during hemodialysis. The degree of leukopenia was moderate (-22%) and comparable with Polysulfone 600 (-25%). C3a desarg generation had a tendency to be lower with the Polyflux 130 membrane, and C5a desarg formation was identical with both types of membranes. As for degranulation of polymorphonuclear leukocytes, plasma elastase levels increased by 209% with Polyflux 130 and by 160% with Polysulfone 600 membranes. Likewise, plasma lactoferrin values rose during hemodialysis by 233% (Polyflux 130) and 160% (Polysulfone 600). The differences between membranes, however, were statistically not significant. There was a sharp drop in the serum levels of beta 2-microglobulin during dialysis with both membranes (Polyflux 130: -46%; Polysulfone 600: -48%). Accordingly, sieving coefficients were calculated to be 0.77 +/- 0.06 for Polyflux 130 and 0.80 +/- 0.06 for the Polysulfone 600 membrane. Both membranes were capable to remove large quantities of beta 2-microglobulin, amounting to 235 +/- 11 and 250 +/- 10 mg/4 h of dialysis for Polyflux 130 and Polysulfone 600, respectively.

Topics: Adult; Amyloidosis; beta 2-Microglobulin; Cellulose; Complement Activation; Evaluation Studies as Topic; Humans; Lactoferrin; Leukopenia; Membranes, Artificial; Middle Aged; Nylons; Pancreatic Elastase; Polymers; Renal Dialysis; Sulfones; Uremia

The effect of the calcium channel blockers nifedipine (9 and 18 micrograms kg-1 h-1), diltiazem (100 and 200 micrograms kg-1 h-1) and verapamil (19 micrograms kg-1 h-1) continuously infused during haemodialysis on granulocyte and complement activation was investigated. Plasma levels of lactoferrin, elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI) and C3a were measured in patients dialysed with dialysers made of cuprophane, polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN). Calcium channel blockers caused no change of blood pressure during haemodialysis in all patients. There was no effect of nifedipine, diltiazem or verapamil on plasma lactoferrin, E-alpha 1PI or C3a levels in patients dialysed with cuprophane. However, plasma lactoferrin and E-alpha 1PI values were significantly reduced by all calcium channel blockers in patients dialysed with PMMA, and also by nifedipine and verapamil in patients dialysed with PAN. Our data indicate that calcium channel blockers inhibit granulocyte activation occurring in dialysers with very little anaphylatoxin formation. These drugs, however, are ineffective in patients dialysed with cuprophane where complement activation takes place. Therefore, granulocyte activation during haemodialysis in the absence of complement activation seems to be mediated by calcium ions.

Topics: Aged; alpha 1-Antitrypsin; Blood Proteins; Calcium Channel Blockers; Complement Activation; Female; Granulocytes; Humans; Kidneys, Artificial; Lactoferrin; Leukopenia; Male; Middle Aged; Pancreatic Elastase; Renal Dialysis; Uremia

Recently, a new type of modified cellulosic membrane (Hemophan) has been made available for the first clinical trials. In contrast to cellulose acetate membranes only about 5% of the hydroxyl groups of cellulose are substituted by tertiary amino groups. Objective of the present study was to assess the compatibility performance of this new membrane material. Therefore, 10 patients were dialyzed consecutively with membranes made of regenerated cellulose (Cuprophan) and modified cellulose. The modified cellulosic membrane showed less leukopenia. The generation of C3adesarg was reduced throughout the dialysis session. Both, the release of lactoferrin and elastase from granulocytes was diminished with the modified cellulosic membrane. All these differences reached the level of significance. Therefore, it seems that with Hemophan a more biocompatible type of cellulosic membrane has been introduced into hemodialysis treatment.

Topics: Biocompatible Materials; Cellulose; Complement Activation; Granulocytes; Humans; Lactoferrin; Leukopenia; Membranes, Artificial; Middle Aged; Pancreatic Elastase; Renal Dialysis; Uremia

Highly purified lactoferrin was obtained from human breast milk by sequential use of affinity chromatography and isoelectric focusing. IgG antibody to purified lactoferrin was used to develop a sensitive and reproducible enzyme linked immunosorbent assay. Characteristics of the assay included linearity over a wide range of lactoferrin concentration (3.125-200 micrograms/l) and sensitivity (lower range less than 1 microgram/l). The assay can be adapted for use on tissue cytosol as well as plasma. Healthy subjects showed plasma lactoferrin levels ranging from 187.5-450.1 micrograms/l. Pulmonary tuberculosis and acute pneumonia are associated with a 2-3-fold increase in plasma lactoferrin content while neutropenic subjects have markedly depressed lactoferrin concentrations. The assay will be useful for further delineation of lactoferrin and neutrophil function and turnover.

Topics: Antibodies; Arthritis, Rheumatoid; Breast Neoplasms; Cytosol; Edetic Acid; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lactoferrin; Lactoglobulins; Leukopenia; Male; Milk, Human; Pneumonia, Pneumococcal; Tuberculosis, Pulmonary