Comparative evaluation of macrophage stimulation and depression on tumor growth and macrophage content and function in mice

Summary In a syngeneic murine adenocarcinoma model, the administration of glucan, an RE stimulant, inhibited tumor growth and increased tumor macrophage populations. Conversely, the administration of methyl palmitate, an RE depressant, potentiated tumor growth and decreased the number of tumor macrophages. Glucan and methyl palmitate also produced diverse alterations in serum lysozyme levels that reflected their contrasting influences on RE functional status, thus supporting the role of serum lysozyme as an index of macrophage function. The diverse results produced by macrophage stimulation or depression in regard to tumor growth, tumor macrophage population, and serum lysozyme concentration indicate that a relationship may exist between macrophage functional activity and host resistance to neoplasia.     

Humoral factors in the regulation of the natural resistance of the body in toxic lesion of the liver]

The dynamics of natural resistance factors (complement, lysozyme, the bactericidal potency of blood serum) were found to be similar in rabbits with the toxic lesions of the liver resulting from the administration of carbon tetrachloride and in intact homologous rescipients receiving the serum of poisoned animals. Simultaneously a decrease in the complement titre and an increase in lysozyme activity and in the bactericidal potency of blood serum were observed. The effect thus revealed could be suppressed by treating the serum with contrical, a polyvalent proteinase inhibitor.     

The effect of temperature on non-specific defence parameters of three strains of juvenile Atlantic halibut (Hippoglossus hippoglossus L.)

The effect of temperature (8, 12, 15 and 18 degrees C) on a variety of non-specific defence and haematological parameters was examined in three geographically distinct reared strains (Canadian, Icelandic, Norwegian) of Atlantic halibut. The results indicate that temperature exerts a considerable influence on some blood parameters (packed cell volume and the percentage population of leucocytes in peripheral blood) and on some humoral parameters (serum lysozyme activity and serum protein levels) of halibut. A high temperature of 18 degrees C caused a decrease in the number of circulating blood cells and an increase in serum lysozyme levels; effects consistent with those reported within the literature for stress. The different strains of halibut exhibited differing responses with respect to differential counts of peripheral blood lymphocytes and thrombocytes, and to serum protein concentrations, serum lysozyme activity, serum iron content, unsaturated iron binding capacity of serum and O2- production by kidney macrophages.     

Lysozyme activity in the leukocytes and blood serum of white rats administered massive doses of penicillin preparations]

Activity of lysozyme in the blood serum and leucocytes was determined. The experiments were carried out on albino unbred rats weighing 170 to 200 gm. Benzylpenicillin and oxacillin were administered intramuscularly in doses of 500000 Units/kg or 20000 gamma/kg once every 24 hours for 2, 4 and 6 days. The activity of lysozyme was determined by the turbidimetric and agar-diffusion methods. It was found that the activity of lysozyme in the leucocytes increased by the 5th day accompanied by a simultaneous decrease in its level in the serum followed by reaching the initial values. The data are indicative of the fact that the use of antibiotics in mega-doses is not contraindicated from the point of view of their effect on lysozyme activity.     

Efficient use of a combination of ampicillin and chymotrypsin]

The effect of chimotripsin on the level and duration of the ampicillin concentration increase in rats, as well as the effect of the enzyme on the in vitro antibiotic detection in the blood serum and organ homogenates of the animals was studied. It was found that rational combined use of ampicillin and chimotripsin required the enzyme administration not later than 1 hour before the antibiotic injection. Chimotripsin provided increased ampicillin levels in the blood serum and liver of the rats for at least 5 hours and in the kidneys and lungs for at least 4 hours. The enzyme present in the rats for 2 hours had no effect on determination of ampicillin activity in vitro in the presence of the blood serum and organ homogenates of the animals.     

Nonspecific resistance in germ-free and E. coli monocontaminated miniature piglets]

Phagocytic activity of leukocytes, as well as the complement, properdin, and lysozyme levels in the blood serum of miniature piglets, germfree and monocontaminated with E. coli 055 and E. coli 083, were studied. E. coli 055 phagocytosis was decreased in the presence of autologous serum and complement and increased under the effect of specific opsonins (antibodies to E. coli 055). Complement, properdin, and lysozyme levels were decreased in the germfree, in comparison with conventional animals. In the E. coli contaminated piglets properdin and complement production was stimulated most, and lysozyme formation--less. No antibodies to E. coli 055 were revealed in monocontaminated piglets. The highest lysozyme levels were found in the ex-germfree animals, this indicating the participation of factors other than E. coli contamination in lysozyme stimulation. It is concluded that microbial contamination played an important role in the development of cellular and humoral factors of the organism resistance.     

Immunocytochemical observations on the organ distribution of exogenous monomeric and dimerized lysozyme.

Using commercial anti-lysozyme antibodies and anti-dimerized lysozyme rabbit serum produced by us we demonstrated by immunohistochemistry, in some organs of rats, the expression of exogenous egg white lysozyme preparations beside the native lysozyme. After oral administration, the egg white lysozyme was detected in intestinal epithelium, proximal and distal tubules of some nephrons, pulmonary alveolar walls and hepatocytes in the 3rd zone of liver acini, whereas native lysozyme was strongly expressed in intestinal and pulmonary macrophages in both the experimental and control animals. However, expression of the dimerized lysozyme released from the intraperitoneally implanted mini-osmotic pumps and detected using specific antisera was evident only on erythrocytes in intestinal blood vessels. It is concluded that the lysozyme preparations administered per os or parenterally are resorbed to blood circulation and distributed among various organs in an active form and maintaining their antigenic specificity. It may speak for their direct anti-inflammatory and immunomodulatory effects in respiratory, urinary, digestive and other systems.     

Humoral factors of transplantation immunity in carp]

The levels of isohemagglutinins, isohemolysins, heterohemagglutinins and lysozyme in blood serum of one and half year old carps have been fixed after scales transplantation. Since three weeks after grafting isohemagglutinins and isohemolysins were revealed in recipient fishes with the prevalence of 25% and 95% respectively. Intact carps from the same group were lack of these antibodies. Recipient and intact fishes did not differ reliably by heterohemagglutinins and lysozyme level in the blood serum. There was no correlation between destroyed allografts share and hemolysins titre of serum, so the double role of humoral antibodies in grafting immunity in carps can be assumed.     

CANADIAN MEDICAL NEWS

Using the radioimmunoassay technique for measuring serum digoxin, it was found that patients who were given 0.25 mg. digoxin orally per day had a mean serum level of 0.83 ± 0.06 ng. per ml. In patients given 0.5 mg. daily the mean level was 1.30 ± 0.14 ng. A higher 24-hour urinary excretion of digoxin was associated with the higher serum levels in the latter group. Individuals who exhibited electrocardiographic evidence of digoxin toxicity had a mean serum level of 2.81 ± 0.21 ng. The majority of patients with high serum levels had evidence of impaired renal function, and it is in this clinical situation that knowledge of serum digoxin levels is likely to be most helpful in determining dose schedules.The method is specific, sensitive and reproducible. Repeated measurements on the same patient on maintenance therapy showed little variation. To obtain dependable serum levels blood should be drawn at least five hours after oral, and three hours after intravenous administration.     

Serum lysozyme in mice subjected to combined immunosuppression with 6-mercaptopurine and hydrocortisone

Simultaneous peroral administration of 6-mercaptopurine (80 mg/kg per day) and subcutaneous injection of hydrocortisone (1 mg/mouse per day) for ten days results in increased lethality and more pronounced decrease in total peripheral leukocyte count and serum lysozyme levels as compared with mice receiving each drug separately. The possible mechanism of this effect is discussed.     

Pharmacokinetics of penicillins in the blood of dogs administered the combination preparation, ampiox, internally]

The pharmacokinetics of penicillins in the blood of dogs treated with ampiox, a combination of ampicillin and oxacillin at a ratio of 1 : 1 was studied. The drug was administered orally in single or repeated doses of 25, 50 and 100 mg/kg. The maximum levels of ampicillin in the blood serum were observed 1 hour after a single administration of the drug. The therapeutic concentrations of the antibiotic were preserved for 6 hours, its value being depended on the dose used. The maximum concentration of oxacillin was detected 1 hour after the drug administration in various doses and it was preserved in the blood at the therapeutic levels for 3 hours. The dynamics of circulation of ampicillin and oxacillin administered separately did not differ from that established for the use of ampiox. The regularities of the pharmacokinetics of ampiox on its repeated use remained practically unchanged.     

Peculiarities of the lysozyme content in cods (order Gadiformes) and flatfish (order Pleuronectiformes)

There was analyzed the content of lysozyme-the parameter of the non-specific immunity-in kidney, liver, spleen, and blood serum in 8 fish species of orders Gadiformes and Pleuronectiformes. The cods are characterized by very low level of the enzyme or by the absence of its activity in some organs and in blood serum regardless of the fish habitat. The flatfish demonstrated diversity in the content and distribution of lysozyme in the body of fish of different species. Two flatfish species inhabiting the Okhotsk Sea, with the unique distribution of the enzyme, are revealed. Their peculiarity is due, first, to the highest content of lysozyme in the blood serum among all fish studied earlier; second, to exceeding 2–3 times the enzyme amount in blood serum, as compared to the studied immunocompetent organs. The obtained results confirm the concept that among the fish there exist different related groups differing by the lysozyme activity, and, possibly, by peculiarities of the non-specific immunity as a whole.     

Effect of gentamycin in combination with prodigiozan on the immunological reactivity of the body

The effect of gentamicin sulphate and its combination will prodigiozan on antibody formation in experiments and the levels of the immunobiologic reactivity of patients with purulent inflammatory processes was studied with a purpose of developing rational schemes of antibiotic therapy of infectious diseases. A decrease in the titers of the antibodies to Aeromonas and the number of antibody-forming cells in the spleen was noted on repeated administration of gentamicin to albino mice in a dose of 20 mg/kg. This was prevented by the use of prodigiozan in a dose of 500 micrograms/kg once every 4 days. The use of gentamicin in patients with purulent inflammatory diseases in doses of 40 or 80 mg twice a day for 7--10 days had no significant effect on the titers of IgA, IgG, IgM, lysozyme blood serum levels, serum bactericidal activity and absorption activity of the peripheral blood neutrophils. Still, it induced a marked suppression of the neutrophil digestive capacity as compared to the initial levels, especially on administration of gentamicin in a dose of 40 mg twice a day. An increase in the level of IgM and no suppression of the neutrophil digestive capacity were noted after completion of the therapy in the patients treated with gentamicin administered in a dose of 40 mg twice a day and prodigiozan administered in a dose of 50 micrograms once every 4 days. It is recommended to use prodigiozan in combinaed therapy with gentamicin for correction of the changes in the specific and nonspecific protective forces of the host.     

Changes in serum lysozyme activity in terminal states caused by blood loss]

A study was made of the dynamics of the lysozyme activity of the serum in dogs which sustained clinical death on the background of a 2-hour hypovolemic hypotension due to blood loss. There was revealed a progressive increase in the lysozyme activity of the serum during the hypotension and during the first 30 minutes of the postreanimation period. Lysozyme activity of the serum was increased in the course of 4 days after the revival. The significance of the lysozyme activity of the serum as an index of hypoxic injury of the internal organs in terminal conditions is discussed.     

Effect of levamisole on alpha 2-macroglobulin and lysozyme levels in the trachea, peritoneal exudate and serum of mice

Levamisole was studied for its effect on alpha 2-macroglobulin and lysozyme content in the blood serum, peritoneal exudate, tracheal extracts of mice. Dynamics of changes in the content of these proteins was studied with its significant increase depending on the methods of the preparation administration (inhalation; intraperitoneal and per os).     

Assay of ethynyloestradiol in human serum and its binding to plasma proteins

A radioimmunoassay for estimating both unconjugated and conjugated ethinyl estradiol (EE) in serum is described, along with a report of levels of EE attained after its administration and the binding of EE in plasma, as determined by this radioimmunoassay. Mean values for concentration of free EE were 38-87 pg/ml, 1-4 hours after administration, and by 24 hours levels in most subjects were below the sensitivity level of this assay, which is less than 25 pg/ml. Conjugated EE concentration in serum was considerably higher, with mean values of 370-770 pg/ml 1-4 hours after ingestion, decreasing slowly to mean values of 285 pg/ml at 8 hours and 100 pg/ml at 24 hours postadministration. Total EE (conjugated plus unconjugated) had a mean half-life of 3.8 hours during the period 2-8 hours after administration and 10.7 hours for the period 8-24 hours postadministration. EE in plasma was shown, by equilibrium dialysis, gel filtration on Sephadex G200, and polyacrylamide gel electrophoresis, to bind only to albumin, and no specific binding of EE occurred. The apparent association constant for the binding of EE to human serum albumin was 1.7 times 10 5 liter per mol.     

Transient lysozymuria during Sarcoma I tumor rejection

The present studies on the in vivo regulation of lysozyme synthesis by cytotoxic macrophages infiltrating Sarcoma I (Sa I) tumor ascites of C57BL/KS mice are an extension of previous observations that the elevation of serum and urinary lysozyme levels might reflect the degree of macrophage-mediated host resistance. Cytotoxic macrophages of host origin are required in the natural rejection of tumors by C57BL/Ks mice challenged with Sa I. The amounts of lysozyme in the serum and urine of the affected mice are quantitated during Sa I growth and rejection. The enzyme levels are correlated with the number of macrophages in the tumor and with the capacity for lysozyme synthesis measured in vitro on monolayers of macrophages isolated from the ascites. The results indicate that the elevation of serum and urinary lysozyme activity is a reflection of both the increased number of cytotoxic macrophages in the host and the qualitative change in the functional state of the cells. These parameters alone cannot account for the extent of the in vivo release of lysozyme in the serum and urine of the affected animals. High levels of lysozyme are present in the extracellular fluids of the mice only when the macrophages are actively participating in host defense. We conclude that in vivo control mechanisms which depend on the presence of viable tumor cells are responsible for the regulation of lysozyme release by cytotoxic macrophages. However, the high levels of lysozyme do not always indicate complete rejection, as indicated by a preliminary observation in which extensive lysozymuria was followed by tumor relapse.     

IgG,IgA, and lysozyme in Martina Franca donkey jennies and their foals

Because immune transfer from jenny to donkey foal is mostly unknown, the aim of the present study was to evaluate, from 5 days before to 10 days after foaling, immunoglobulin (Ig)G, IgA, and lysozyme peripartal concentrations in serum and mammary secretions of 10 healthy, spontaneously foaling Martina Franca jennies and in serum of their mature, viable, healthy foals, in the first 10 days after birth. The results showed that, in jennies, mammary secretion of IgG levels (ranging between 16 and 75 mg/mL) and IgA (0.9–2 mg/mL), and IgG (6.8–13.5 mg/mL) and IgA (0.5–2.4 mg/mL) serum concentrations were not different along the time of study. Also, IgG concentrations in serum of foals did not show significant differences although a high level was observed at 12 hours after birth (8 mg/mL), and IgA concentrations in serum of foals did not show any significant difference, although a high level was observed at 12 hours after birth (1.2 mg/mL). Lysozyme increased significantly at Day 2 after parturition in mammary secretions of jennies (551.9 μg/mL) and at 12 hours in serum of foals (25.9 μg/mL). The study demonstrated that the pattern of passive immune transfer in donkey foals seems to be similar to that reported for the horse foal, with IgG predominating IgA in serum and mammary secretions of the jenny and also in serum of foals. The most significant early increase in foals' serum concerns lysozyme, which probably plays an important role in the innate immunity of the donkey foal in the first challenging hours after birth.     

57Co-bleomycetin pharmacokinetics in the body of mice with LIO-1 lymphosarcoma

Pharmacokinetics of 57Co-bleomycetin was studied on mice with lymphosarcoma LIO-1. It was found that at early periods of intravenous administration of the labeled antibiotic, i.e. within the period from 5 minutes to 1 hour its higher levels are detected in the liver, kidneys, blood serum, lungs, intestine and tumor. At later periods the drug levels in the organs and tissues gradually decrease and by the 72nd hour the concentration of 57Co-bleomycetin in the blood serum appears to be 30 times lower as that after 5 minutes. In the muscles and tumor its concentrations by that period are 15 and 2 times lower respectively. Radiometry of the animals showed that within the first 24 hours more than 85 per cent of 57Co-bleomycetin was excreted from the mice.     

Nasal insulin gel as an alternate to parenteral insulin: Formulation,preclinical, and clinical studies

The objective of the present study was to formulate insulin gel for intranasal administration and to evaluate with respect to in vitro release studies and hypoglycemic activity in animal model and healthy human volunteers. The insulin gel was formulated using the combination of carbopol and hydroxypropyl methylcellulose as gelling agent. The in vivo efficacy of insulin gel administered intranasally was assessed by measuring the blood glucose levels and serum insulin levels at specified time intervals in rats and humans. The use of bioadhesive nasal gel containing insulin not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity but also facilitated direct absorption of medicament through the nasal mucosa. Absorption of the drug through the nasal mucosa was high in the first 0.5 to 1.5 hours of the study with a sharp decline in blood sugar and rise in insulin values corresponding to that decline in blood sugar. This study further demonstrates that administration of insulin intranasally in gel form is a pleasant and painless alternative to injectable insulin. Published: September 30, 2005.