lactoferrin and Hemorrhage

Strongly pronounced argyrosis caused by adding AgCl to the feed of laboratory rats efficiently mimics the deficiency of ceruloplasmin (CP) ferroxidase activity. Bringing the concentration of AgCl in the feedstuff of lactating rats to 250 mg % and keeping their progeny (Ag-rats) for 3 months on the same silver-containing feed provided the serum iron content 1.4 times lower than that in the control group. Besides, the ferroxidase activity of CP dropped to zero. In CP purified from sera of Ag-rats two copper ions were substituted with two silver ions. Using rat models of both post-hemorrhagic and hemolytic anemia we showed that the deficiency of CP ferroxidase activity in Ag-rats affects the iron content in serum, though does not prevent the recovery of hemoglobin level accompanied by exhaustion of iron caches in liver and spleen. When apo-lactoferrin (apo-LF) was administered to Ag-rats suffering from either post-hemorrhagic or hemolytic anemia, both hemoglobin and serum iron were restored more rapidly than in the control animals. In independent experiments Ag-rats were compared with those fed on regular diet and the former displayed a prolonged 3-day stabilization of hypoxia-inducible factors 1 and 2 alpha (HIF-1a and HIF-2a) along with an increased serum concentration of erythropoietin. Introduction to Ag-rats of active CP separately or together with apo-LF reduced that effect to 1 day only. It is concluded that saturation of apo-LF with iron, provided by active CP, can strongly affect its protective capacity.

Topics: Acute Disease; Anemia; Animals; Ceruloplasmin; Diet; Female; Hemorrhage; Iron; Lactoferrin; Rats; Rats, Wistar; Silver Compounds

Lactoferrin (LF) plays various anti-inflammatory roles in inflammation experimentally induced by lipopolysaccharides (LPS). But the protective effects of LF on LPS-induced acute lung injury (ALI) have not been elucidated. In this study, we aimed to study the effects of LF on ALI caused by LPS in mice. At 1h before or after LPS injection, an intraperitoneal injection of LF (5mg/body) was administered. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analyses 12h after LPS exposure. We found that both prophylactic and therapeutic administration of LF significantly decreased the W/D ratio of the lung and protein concentration in the BALF. LF significantly reduced the pulmonary myeloperoxidase activity and the number of total cells in the BALF 12h after LPS challenge. LF treatment markedly attenuated lung edema, alveolar hemorrhage and inflammatory cells infiltration. Moreover, LF also decreased the production of TNF-α and increased interleukin-10 in the BALF. These results firstly indicate that LF may protect against LPS-induced ALI in mice.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Hemorrhage; Interleukin-10; Lactoferrin; Lipopolysaccharides; Lung; Male; Mice; Neutrophils; Peroxidase; Pulmonary Edema; Tumor Necrosis Factor-alpha

Salivary lactoferrin is a glycoprotein involved in the elimination of pathogens and the prevention of massive overgrowth of microorganisms that affect oral and general health. A high concentration of lactoferrin in saliva is often considered to be a marker of damage to the salivary glands, gingivitis, or leakage through inflamed or damaged oral mucosa, infiltrated particularly by neutrophils. We conducted a study to determine the effect of chronic alcohol intoxication on salivary lactoferrin concentration and output. The study included 30 volunteers consisting of ten non-smoking male patients after chronic alcohol intoxication (group A), and 20 control nonsmoking male social drinkers (group C) with no history of alcohol abuse. Resting whole saliva was collected 24 to 48 hours after a chronic alcohol intoxication period. Lactoferrin was assessed by enzyme-linked immunosorbent assay. For all participants, the DMFT index (decayed, missing, or filled teeth), gingival index (GI) and papilla bleeding index (PBI) were assessed. The differences between groups were evaluated using the Mann-Whitney U test. We noticed significantly decreased salivary flow (SF) in alcohol dependent patients after chronic alcohol intoxication (A), compared to the control group (C). Although there was no significant difference in salivary lactoferrin concentration between the alcohol dependent group A and the control group C, we found significantly decreased lactoferrin output in group A compared to group C. We found a significant correlation between the amount of daily alcohol use and a decrease in lactoferrin output. There was a significant increase in GI and a tendency of PBI to increase in group A compared to group C. We demonstrated that chronic alcohol intoxication decreases SF and lactoferrin output. The decreased lactoferrin output in persons chronically intoxicated by alcohol may be the result of lactoferrin exhaustion during drinking (due to its alcohol-related lower biosynthesis or higher catabolism) or to decreased function of neutrophils affected by the ethanol. The poorer periodontal state in alcohol dependent persons compared to controls may be a result of lower salivary flow and decreased protection of the oral cavity by lactoferrin.

Topics: Adult; Alcohol Drinking; Alcoholism; Dental Papilla; Female; Hemorrhage; Humans; Lactoferrin; Male; Middle Aged; Periodontal Index; Saliva; Statistics, Nonparametric

We evaluated the characteristics of seminal vesicle amyloidosis (SVA) associated with hemospermia by immunohistochemistry and magnetic resonance imaging (MRI) as well as the clinical course of hemospermia.. Of 56 patients with hemospermia 12 underwent transperineal biopsy of the seminal vesicle under transrectal ultrasound monitoring. SVA was proved in 4 men 48 to 59 years old by histological and immunohistochemical examinations of specimens obtained by biopsy. Two men presented with the first episode of hemospermia and 2 presented with recurrent hemospermia. MRI at 1.5 Tesla was performed while hemospermia persisted and after its resolution. Patients were followed for 10 to 86 months with regard to the duration of hemospermia, the time of its resolution and its recurrence.. Amyloid deposits in the subepithelial tissue of the seminal vesicles were permanganate sensitive, and positive for lactoferrin and the amyloid P component but negative for amyloid A protein, lambda and kappa chains, and beta2-microglobulin. The seminal vesicles with obvious intravesicular hemorrhage on needle puncture were hyperintense on T1-weighted images. After hemospermia resolution T1-weighted images became diffusely hypointense. T2-weighted images were of low intensity, representing amyloid deposits. Hemospermia resolved spontaneously in all patients in an average of 14 months. Although disease recurred in 1 patient after 8 months of resolution, it disappeared after 11 months of recurrence.. Localized SVA with hemospermia shows hypointensity on T2-weighted MRI. Hemospermia is spontaneously resolved with the transition from hyperintense to hypointense T1-weighted MRI.

Topics: Amyloid; Amyloidosis; beta 2-Microglobulin; Biopsy, Needle; Blood; Epithelium; Follow-Up Studies; Genital Diseases, Male; Hemorrhage; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunohistochemistry; Lactoferrin; Magnetic Resonance Imaging; Male; Middle Aged; Recurrence; Remission, Spontaneous; Semen; Seminal Vesicles; Serum Amyloid A Protein; Serum Amyloid P-Component; Ultrasonography, Interventional

Isoproterenol hydrochloride (ISO), a beta adrenergic agonist, is known to cause ischemic necrosis in rats. Cardiotoxicity of three different doses of ISO were studied using physiological, biochemical and histopathological parameters. The effects of single and double dose of ISO were analysed, which illustrated that single ISO dose was more cardiotoxic than double ISO dose due to ischemic preconditioning. The tetrapeptide derivatives L-lysine-L-arginine-L-aspartic acid-L-serine (tetrapeptide A) and di-tert.butyloxycarbonyl-L-lysine-L-arginine-L-aspartic acid-tert.butyl O-tert.butyl-L-serinate (tetrapeptide B) along with acetylsalicylic acid as positive control were analysed at different time points for their cardioprotective effect. The results demonstrated that optimal protective effects were observed by pretreatment with 5 mg/kg of tetrapeptide B and this was found to be slightly better than that of acetylsalicylic acid. A lesser degree of cardioprotection was noticed when low doses of tetrapeptide B were administered. This study clearly showed that single dose of ISO (50 mg/kg, s.c.) induced myocardial necrosis could be used as a model to assess cardiovascular drugs and in this model, it was demonstrated that the tetrapeptide B could exhibit optimal cardioprotective effect.

Topics: Adrenergic beta-Agonists; Animals; Aspirin; Body Weight; Creatine Kinase; Disease Models, Animal; Female; Hemodynamics; Hemorrhage; Isoproterenol; L-Lactate Dehydrogenase; Lactoferrin; Myocardial Ischemia; Myocardium; Necrosis; Oligopeptides; Organ Size; Peptide Fragments; Platelet Aggregation Inhibitors; Rats; Rats, Wistar

We have studied a young male with lactoferrin deficiency and a bleeding tendency responsive to cryoprecipitate. This child has had increased bleeding following surgical procedures and a variably prolonged template bleeding time. The patient has a normal platelet count, normal in vitro platelet ATP secretion and aggregation in response to a variety of agonists, and normal concentration of plasma-von Willebrand factor ristocetin cofactor activity and antigen. Analysis of plasma-vWf multimers by agarose gel electrophoresis consistently demonstrated a subtle decrease in the largest vWf multimers. In contrast, analysis of the patient's platelet-vWf revealed normal vWf:Ag, decreased vWf ristocetin cofactor activity, and a striking absence of the high and intermediate size molecular weight vWf multimers. Analysis of surface bound platelet-vWf demonstrated normal amounts on the surface of unstimulated platelets, but after thrombin stimulation the platelet-vWf surface expression did not increase. This lack of increased platelet-vWf surface expression resulted from decreased binding of secreted platelet-vWf to be surface of stimulated platelets. These data suggest that the patient's bleeding tendency may be related to a defect in his platelet-vWf structure and/or mobilization. This case represents a unique demonstration of an abnormality of platelet-vWf in the presence of normal plasma-vWf, and supports the data indicating an important role for platelet-vWf in primary hemostasis.

Topics: Biopolymers; Blood Platelets; Child; Disease Susceptibility; Hemorrhage; Humans; Lactoferrin; Male; Platelet Function Tests; von Willebrand Factor