Population Pharmacokinetics and Absolute Oral Bioavailability of Lasalocid after Single Intravenous and Intracrop Administration in Laying Hens.

Lasalocid sodium is a polyether carboxylic ionophore agent authorized by the EU for use as a coccidiostat in broilers, turkeys, and pullets up to 16 weeks of age, except for laying hens. However, laying hens are the most common nontarget species exposed to lasalocid sodium, mainly due to cross-contamination from feed mills. This exposure may result in potential drug residue deposition in eggs, which could potentially expose consumers to the drug. The breeds commonly used for commercial egg production in Poland are Isa Brown and Green-legged Partridge hens, which have been found to significantly differ in egg-laying performance. This variability may also affect the pharmacokinetics of lasalocid. Data on lasalocid plasma pharmacokinetics in laying hens are lacking. In this study, we aimed to determine typical population pharmacokinetic parameters, absolute oral bioavailability, and how breed may influence the pharmacokinetics of lasalocid. Twenty-layer hens of the two breeds were used in this study. Lasalocid was administered orally at a single dose of either 1 mg or 5 mg/kg body weight or intravenously at a dose of 1 mg/kg body weight, in a crossover design with a three-week washout period between study periods. Blood samples were collected for 72 h, and lasalocid concentrations were measured using high-performance liquid chromatography with fluorescence detection. A population pharmacokinetic analysis was conducted using nonlinear mixed effects modeling. Standard numerical and graphical criteria were used to select the best model, and a stepwise covariate modeling approach was used to determine any influencing factors. The best model was a three-compartment mammillary model with first-order absorption, transit compartments, and linear elimination. The estimated absolute oral bioavailability was low (36%). It was found that breed significantly influenced not only absorption but also the elimination of lasalocid. This study revealed that lasalocid absorption and elimination varied between the two breeds. This variability in pharmacokinetics may result in breed-related differences in drug residue accumulation in eggs, and ultimately, the risk associated with consumer exposure to drug residues may also vary.

The influence of the site of drug administration on florfenicol pharmacokinetics in turkeys.

Florfenicol is a broad-spectrum antibacterial drug used in the treatment of farm animals, including poultry. This drug is poorly soluble in water, therefore, administration in drinking water may lead to high variability of concentrations in treated individuals. The use of injection preparations, however, requires individual administration and may have a negative effect on the quality of the carcass. In addition, the renal portal system in birds may reduce the bioavailability of the drug administered in the caudofemoral region of the body. The aim of this study was to compare the pharmacokinetics of florfenicol in turkeys after a single intravenous, intramuscular, and subcutaneous administration at a dose of 15 mg/kg body weight. Additionally, to evaluate the effect of renal portal system on drug kinetics, the intramuscular administration was divided into pectoral and caudofemoral administration. The study showed that the area under the concentration-time curve (AUC) was similar regardless of the route of administration. The mean values for clearance and volume of distribution were 0.33 L/kg/h and 0.92 L/kg, respectively. The mean residence time (MRT) was 2.87 h for an intravenous bolus, while for the extravascular administrations it was approx. 5.5 h. The elimination half-life was approx. 4 h regardless of the route of administration. The maximum plasma concentration did not differ statistically between intramuscular (approx. 6.8 mg/L) and subcutaneous (8.2 mg/L) administrations, while the time to appear for this concentration was the longest for caudofemoral administration (1.5 h). The bioavailability was 88.64% for subcutaneous administration, 77.95% for pectoral administration and 85.30% for caudofemoral administration. Overall, all 3 routes of extravascular administration allowed for efficient drug absorption. There was no evidence of an influence of the renal portal system on the kinetic parameters of the drug administered to the lower extremities of the body.

Pharmacokinetics of florfenicol and thiamphenicol after single oral and intravenous, as well as multiple oral administrations to geese.

1. This study evaluated the pharmacokinetic profiles of florfenicol (FF) and thiamphenicol (TP), which are synthetic bacteriostatic antimicrobial drugs, in geese after a single intravenous or oral administration, as well as seven oral doses administered at 12 h intervals. For all treatments, the dose was 30 mg/kg. 2. After single IV administration, clearance and volume of distribution were low (0.23 ± 0.03 l/h/kg and 0.57 ± 0.08 l/kg for FF, and 0.23 ± 0.04 l/h/kg and 0.59 ± 0.08 l/kg for TP, respectively). The elimination half-life was similar between products and short (2.91 ± 0.41 and 2.84 ± 0.64 h for FF and TP, respectively). 3. The single oral administration resulted in efficient absorption (bioavailability of 83.15 ± 11.48 for FF and 75.21 ± 19.56% for TP) with high maximal concentrations of 30.47 ± 2.47 and 20.02 ± 3.87 µg/ml for FF and TP, respectively. The area under the curve was 108.36 ± 14.96 and 101.81 ± 26.48 mg×h/l for FF and TP, respectively. 4. For both drugs, the two latter parameters were found to be higher compared to earlier studies on terrestrial birds. This suggested that FF and TP may be efficient in treating infections in geese caused by certain bacteria sensitive to chloramphenicol. 5. Neither drug accumulated in tissues following the oral seven doses and no adverse effects were noted in any treated animals. Thus, the selected FF and TP dosage may be considered as a safe treatment for geese.

Modulation of lymphocyte subsets and humoral immune response by florfenicol administered to sheep red blood cell-immunized broiler chickens.

Florfenicol is a broad-spectrum bacteriostatic antibiotic commonly used for the treatment of systemic infections in farm animals. The aim of this study was to determine the effect of florfenicol on the percentage of T lymphocytes (CD3+, CD4+, CD8+, TCRgd+ cells) and B lymphocytes (Bu-1+ cells) and on total serum anti - sheep red blood cell (SRBC) haemagglutinin titer in the peripheral blood of SRBC-immunized broiler chickens. The study included three groups of broiler chickens differentiated by weight (0.5, 1.2, 2.4 kg). Florfenicol was administered orally at a dose of 30 mg/kg. The drug was administered eight times at 24 h intervals. The chickens were immunized with SRBC 24 h after administration of the third dose of florfenicol. Florfenicol increased the percentage of CD3+ blood lymphocytes with a corresponding decrease in the percentage of B lymphocytes in birds weighing 0.5 and 2.4 kg. Florfenicol reduced the production of total anti SRBC-haemagglutinins on day 5 after antigen injection in all three body weight groups of the broiler chickens. In conclusion, florfenicol exerted a modulating effect on the immune response of the birds and this should be taken into consideration when using this antibiotic for certain indications.

The influence of rapid growth on sodium salicylate pharmacokinetics in male turkeys.

The aim of this study was to assess the influence of growth on the pharmacokinetics of sodium salicylate (SS) in male turkeys. SS was administered intravenously at a dose of 50 mg/kg. Plasma drug concentrations were assessed by high-performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. As the age increased from 6 to 13 weeks (body weight increase from 2.35 to 9.43 kg), median body clearance decreased from 1.34 to 0.87 ml/min/kg. This caused a significant increase in the median mean residence time from 3.42 to 4.44 hr. Elimination phase proved to be biphasic and two elimination half-lives (T1/2el ) were distinguished. Whereas T1/2el1 was found to increase with age by 128%, T1/2el2 represented a later but faster and less age-dependent phase of elimination (increase by 56% in the respective groups). Volume of distribution decreased with age. These effects may lead to different therapeutic response to SS in turkeys of different age and body weights.

The influence of growth and E. coli endotoxaemia on amoxicillin pharmacokinetics in turkeys.

1. This experiment aimed to determine if the pharmacokinetics of amoxicillin (AMO) was affected by rapid growth or intravenous (i.v.) injection of Escherichia coli lipopolysaccharide (LPS). 2. Turkeys of 2.0, 5.5 and 12.0 kg were administered i.v. or orally with AMO sodium at the dose of 15 mg/kg. Another group (5.7 kg) was treated with LPS prior to i.v. AMO administration. Plasma drug concentrations were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using a non-compartmental model. To assess the haemodynamic effects of endotoxaemia, turkeys were subjected to echocardiography. 3. During growth from 2.0 to 5.5 kg, the area under the drug concentration-time curve after i.v. AMO administration increased from 9.37 ± 2.43 to 21.29 ± 5.49 mg×h/ml. Total body clearance decreased from 1.72 ± 0.55 to 0.75 ± 0.12 l/h/kg. Growth to 12.0 kg did not further affect these parameters. Mean residence time and elimination half-life gradually increased. Pharmacokinetics of orally administered drug followed a similar pattern. LPS injection affected stroke volume, heart rate and resistance index. However, it did not affect the pharmacokinetic profile of AMO in survivors. 4. It is concluded that rapid growth in turkeys affects AMO pharmacokinetics. Endotoxaemia, on the other hand, does not affect AMO elimination if compensatory mechanisms develop.

The influence of rapid growth in broilers on florfenicol pharmacokinetics - allometric modelling of the pharmacokinetic and haemodynamic parameters.

1. The aim of this study was to determine if the pharmacokinetics (PK) of florfenicol (FF) undergo age-dependent changes in broilers. Since drug elimination depends on cardiovascular functions, a haemodynamic study was performed in parallel. 2. Broilers of 0.68, 1.27, 2.45 and 5.13 kg were administered FF in a single intravenous dose of 30 mg/kg body weight. Plasma drug concentrations were determined using high-performance liquid chromatography and PK parameters were calculated using a non-compartmental model. Echocardiography was used to measure haemodynamic functions. 3. During growth, the area under the drug concentration-time curve (AUCinf) increased from 25.7 ± 2.9 to 39.0 ± 8.0 mg h/l. Total body clearance (ClB) gradually decreased from 1.19 ± 0.14 to 0.80 ± 0.15 l/h/kg. Elimination half-life increased from 0.73 ± 0.08 to 1.07 ± 0.07 h, whereas volume of distribution (Vss) remained unchanged. Haemodynamic measurements revealed an increase in cardiac output, from 495 ± 65 to 1303 ± 306 ml/min, in the respective body weight groups. 4. Allometric models for PK and haemodynamic parameters were developed and validated. All models proved to be statistically significant; however, only models for ClB and Vss met stringent validation criteria. Model for ClB was used to calculate an optimal dose for a given age group that provides uniform AUCinf. 5. Age-dependent change in FF kinetics may cause variability in therapeutic response under clinical conditions. A novel approach to the dosing protocol was proposed as a means of optimising therapeutic efficacy.

Metronidazole pharmacokinetics during rapid growth in turkeys - relation to changes in haemodynamics and drug metabolism.

Whereas interspecies variation in pharmacokinetics is a commonly investigated issue, variations in drug kinetics within a species are less documented. The aim of the study was to assess the influence of age-related changes in haemodynamics on the pharmacokinetics of metronidazole (MTZ) and its hydroxy metabolite (MTZ-OH) in turkeys. MTZ was administered intravenously and orally at a dose of 25 mg/kg. Plasma drug and metabolite concentrations were assessed by high-performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. Haemodynamic parameters (heart rate, stroke volume, cardiac output) were assessed by echocardiography and extraction ratio for MTZ was calculated based on total body clearance (ClB ). Between the 5th and 15th week of age, ClB of MTZ decreased from 3.6 to 1.2 mL/min/kg causing a twofold increase in the mean residence time (MRT) and elimination half-life (T1/2el ). The MTZ-OH production decreased threefold and its MRT and T1/2el increased. Although heart rate significantly decreased with age, cardiac output increased. Extraction ratio was low in all age groups. It is concluded that significant age-dependent decrease in ClB of MTZ in turkeys resulted from decreased perfusion of the clearing organs and their reduced metabolic capacity. This phenomenon is probably species specific and may apply to other therapeutic agents.

Comparative pharmacokinetics of acetylsalicylic acid and sodium salicylate in chickens and turkeys.

1. Pharmacokinetics of acetylsalicylic acid (ASA) and sodium salicylate (SS) were assessed following single intravenous (i.v.) and oral administration at doses of 50 mg/kg body weight to chickens and turkeys. Plasma drug concentrations were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. 2. The mean residence time (MRT) of salicylate (SA) after i.v. administration of SS was 6.08 ± 0.59 and 3.32 ± 0.27 h and after oral administration was 6.95 ± 0.72 and 4.55 ± 0.71 h in chickens and turkeys, respectively. The elimination half-life (T 1/2 e) was shorter in turkeys compared with chickens. The value of body clearance (ClB) was higher in turkeys than in chickens, but the apparent volume of distribution (V ss) was similarly low in both species. The bioavailability of SS was complete and the maximal plasma concentration of SA (C max) after oral administration was 96.93 ± 8.06 and 91.76 ± 9.64 µg/ml, respectively, in chickens and turkeys. 3. The MRT of ASA after iv administration was 0.24 ± 0.08 and 0.24 ± 0.02 h and after oral administration was 0.78 ± 0.25 and 0.59 ± 0.13 h, respectively, in chickens and turkeys. In both species, T 1/2 e was very short, ClB and V ss were similar and markedly higher than those of salicylate. The bioavailability of unchanged ASA was low and C max after oral administration was 6.9 ± 3.6 µg/ml in chickens and 8.6 ± 1.3 µg/ml in turkeys.

Adverse effects associated with high-dose acetylsalicylic acid and sodium salicylate treatment in broilers.

1. Acetylsalicylic acid (ASA) and sodium salicylate (SS) are considered safe for poultry and often used in avian medicine. However, information on tolerance and specific side effects of these drugs in birds is lacking. 2. The aim of this study was to determine the effects of 14 d administration of high doses (200 or 400 mg/kg) of either ASA or SS on body weight gain, blood biochemistry, white and red blood cell counts and pathology in broilers. In addition, minimal plasma salicylate concentrations were determined on the 1st, 5th, 10th and 14th d of treatment. 3. The results showed that the dose of 400 mg/kg of either ASA or SS decreased weight gain and induced gizzard ulceration. Kidney to body weight ratio was increased in a dose-dependent manner, but serum concentrations of creatinine and uric acid were not affected. A time-dependent decrease in the minimal plasma salicylate concentration was evident.

The effects of florfenicol on lymphocyte subsets and humoral immune response in mice.

Florfenicol is a broad-spectrum bacteriostatic antibiotic used in domestic animals. The aim of the study was to determine the effect of florfenicol on the total number of lymphocytes in the thymus, spleen and mesenteric lymph nodes and the percentage and the absolute number of T cell subsets (CD4+CD8+, CD4-CD8-, CD4+, CD8+) in the thymus and T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in the peripheral lymphatic organs in non-immunized mice and humoral immune response in sheep red blood cells (SRBC)-immunized mice. Florfenicol was administered orally at a dose of 30 mg/kg six times at 24 h intervals to non-immunized mice and four or seven times at 24 h intervals to SRBC-immunized mice. SRBC was injected 2 hours prior to the first dose of the drug. Florfenicol increased the percentage of CD4CD8- thymocytes and the absolute number of CD4+ and CD8+ thymocytes on day 7. The increased percentage and absolute number of CD3+, CD4+ and CD8+ lymphocytes in mesenteric lymph nodes and decreased percentage of lymphocytes B were also observed 24 hours from the last administration of florfenicol. Florfenicol administered after SRBC immunization reduced the number of plaque forming cells (PFC) and the production of anti-SRBC antibodies on days 4 and 7 after priming.

Soluble HLA-G is an independent factor for the prediction of pregnancy outcome after ART: a German multi-centre study.

BACKGROUND: Soluble HLA-G (sHLA-G) has been suggested as a non-invasive marker for embryo selection to improve pregnancy rates after assisted reproduction technique (ART). Our study aimed at the identification of parameters influencing the detection of sHLA-G in embryo cultures (ECs) and at the prognostic relevance of sHLA-G in a multi-centre study. METHODS: In total 4212 EC from 2364 cycles were randomly collected from 29 German ART centres and analysed for sHLA-G by Luminex-based technology. RESULTS: Among test and culture conditions, only the cleavage stage of the embryo was identified as an independent factor for sHLA-G detection (P < 0.001). Overall, sHLA-G was significantly associated with pregnancy after ART [P < 0.001; odds ratio: 2.0 (95% CI: 1.7-2.4)], suggesting that sHLA-G testing might improve the pregnancy rate from 30 to 40%. Importantly, the sHLA-G status of embryos could be associated with pregnancy after single embryo transfer [P = 0.002; odds ratio: 3.3 (95% CI: 1.5-6.8)] doubling the probability of pregnancy rate to 26% after sHLA-G testing. The patient's age, number of transferred embryos, morphological grading [EXP(B): 4.3 (95% CI: 2.1-8.9)] of embryos and sHLA-G status [EXP(B): 2.3 (95% CI: 1.8-3.1)] were independent predictors of pregnancy, with the latter two being most powerful. CONCLUSIONS: This study provides significant evidence that the morphological scoring system is still the best strategy for the selection of embryos but that sHLA-G might be considered as a second parameter if a choice has to be made between embryos of morphologically equal quality.

The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia.

Soluble or membrane-anchored ligands of NKG2D and their receptor have a critical role in the elimination of tumor cells and disease progression. Plasma samples of 98 patients with B-cell chronic lymphocytic leukemia (CLL) were analyzed with specific ELISA systems for soluble major histocompatibility complex class I-related chains (sMICA and sMICB) and UL-16-binding proteins (ULBP1, 2, and 3). The flow cytometric analysis of MICA on CLL cells and natural killer group 2 member D (NKG2D) receptors on NK cells was performed after thawing of frozen peripheral blood lymphocytes of CLL patients (N=51). Levels of sMICA, sMICB, and sULBP2 were significantly increased (P<0.001) compared with 48 controls, whereas sULBP1 3 were not detectable in patients and controls. Levels of sMICA>990 pg/ml (P=0.014), sMICB>200 pg/ml (P=0.0001), and sULBP2>105 pg/ml (P<0.0001) were associated with poor treatment-free survival (TFS). Neither MICA nor NKG2D expression could be related to clinical parameters. In multivariate analysis Binet stage (P=0.002), sULBP2 (P=0.002) and ZAP-70 (P=0.002) were independent predictive factors for TFS. In patients with Binet stage A, sULBP2 levels>105 pg/ml were strongly associated (P=0.0025) with poor TFS. Our data show that soluble but not membrane-anchored NKG2D ligands or receptors are of prognostic significance in CLL. Moreover, sULBP2 seems to be useful to identify early-stage patients with risk of disease progression.

Pharmacokinetics of florfenicol, thiamphenicol, and chloramphenicol in turkeys.

The pharmacokinetics of florfenicol (FF), thiamphenicol (TP) and chloramphenicol (CP) after single intravenous (i.v.) or oral (p.o.) administration was studied in an independent cross-over study in broiler turkeys. All the fenicol antibiotics were administered at a dose of 30 mg/kg b.w. and their concentrations in plasma samples were assayed using the same validated high-performance liquid chromatography method. Pharmacokinetic parameters were calculated by a noncompartmental method. The kinetic profiles of the compounds were compared with the results of the structure-activity relationship. According to the proposed mathematical description, no differences in plasma clearance values for the studied antibiotics were observed. The mean residence time values of FF, TF, and CP after i.v. injection were 3.37+/-0.63, 2.43+/-0.29, and 2.12+/-0.21 h, respectively. The mean values of Varea for FF (1.39+/-0.31 L/kg) and TP (1.31+/-0.19 L/kg) were similar, but significantly different from that of CP (1.04+/-0.12 L/kg). The bioavailabilities of FF, TP, and CP after oral administration were 82%, 69%, and 45%, respectively. Differences in the bioavailability values of the compared fenicol antibiotics correspond to the ratio of the apolar/polar surface areas of their particles.

Stationary phase with specific surface properties for the separation of estradiol diastereoisomers.

The aim of this study was to develop a procedure that enabled the separation of estradiol diastereoisomers. For this purpose a series of stationary phases with different surface properties has been utilized. Two of them contain various interaction sites, such as: cholesterol, n-acylamide, amine and silanols localised in the organic layer bonded to the surface of silica gel (SG-CHOL and SG-CHOL/AP). The other one contains mainly alkylamide ligands and also residual aminopropyl and silanol groups (SG-AP), as well as the last one consisting of hydrocarbonaceous material (SG-C(18)). In order to select the best type of stationary phase for this analysis, after chromatographic separation of 17-alpha-estradiol and 17-beta-estradiol, selectivity and resolution of the analytes were compared. The best separation of hormones was obtained for SG-CHOL packing, as a consequence of the structure and the properties of this stationary phase. To better understand the retention mechanism and the properties of the stationary phases, used in the separation of steroid compounds, the functional group contributions (tau) were compared with Hansch substituent constants (pi).

[Disorders of the bone density in the chest x-ray examination in the course of myelosclerosis]. / Zaburzenia utkania kostnego w obrazie radiologicznym klatki piersiowej w przebiegu zwlóknienia szpiku.

The authors report a rare case of myelosclerosis diagnosed during hospital stay in internal Department on account of hepatosplenomegaly and anaemia. The case of patient described by authors was diagnosed on the ground of examination and executed additional investigations: morphology, peripheral blood picture, chest radiography, scintiscan of skeleton.

[Foreign body in the right frontal lobe of the brain as a result of right eyeball and right eye-socket trauma--case report]. / Cialo obce w prawym placie czolowym mózgu w nastepstwie urazu prawej galki ocznej i oczodolu prawego--opis przypadku.

We report a case of a 44 year old man, who was admitted to our hospital because of right eyeball and right eye-socket due to a piece of diamond circular saw. Right eyeball was sutured. CT--examination showed a metallic foreign body in the right frontal lobe of brain. Metallic foreign body, which damaged the right eyeball, caused upper restriction of right eye-socket ceiling and stuck in a frontal lobe of the brain was removed.

Modulation of secondary antibody response in SRBC-immunized mice by lysozyme dimer.

The effect of lysozyme dimer (20 micrograms/kg) injected i.p. once or four times to sheep erythrocytes-immunized mice on the secondary humoral response was studied with respect to the time of exposure to the drug in relation to priming and challenge. It has been found that lysozyme dimer potentiates secondary humoral response to SRBC; as a result, the number of splenocytes producing hemolytic anti-SRBC antibodies (PFC) and anti-SRBC hemagglutinin titers, especially 2-mercaptoethanol resistant increases provided that the drug is administered after the challenge. Lysozyme dimer (both a single dose and four times' exposure to the drug) administered after priming does not affect secondary humoral response of SRBC-immunized mice.

Effects of lysozyme dimer on humoral response to sheep erythrocytes in non-treated and cyclophosphamide-immunosuppressed mice.

The effects of lysozyme dimer on humoral response to sheep erythrocytes (SRBC) and restoration of the response impaired by a single cyclophosphamide dose (200 mg/kg) were tested on mice. The effect of lysozyme dimer on the humoral response to SRBC in non-treated with cyclophosphamide mice was determined in relation to doses (0.2, 2, 20 or 200 micrograms/kg) and the time of the drug administration with respect to the antigen before or after SRBC immunization. Moreover, the effect of lysozyme dimer on the humoral response in cyclophosphamide-treated mice was studied depending on the dose applied and time of exposure to the drug in relation to SRBC. It has been found that lysozyme dimer potentiates the humoral response to SRBC in mice, resulting in an increased number of splenocytes producing haemolytic antibodies (PFC) and the total and 2-mercaptoethanol resistant level of anti-SRBC antibodies. A single exposure to lysozyme dimer gave the strongest stimulating action on SRBC when the doses of 2 or 20 micrograms/kg were administered 2 h prior to the antigen. The potentiating effect of the drug was reduced when it was administered 24 h before the antigen and also when single doses were as high as 200 micrograms/kg and as low as 2 micrograms/kg. Exposure to four doses of lysozyme dimer at 24 h intervals was more activating than a single injection. A strong potentiating effect on the specific response to SRBC was noted after four injections of lysozyme dimer at doses from 0.2 to 20 micrograms/kg. The effect of the drug did not depend on the time of exposure to the antigen. It has also been found that lysozyme dimer significantly reduces the suppressive effect of a high cyclophosphamide dose (200 mg/kg) on the humoral response of SRBC-immunized mice. The protective action of lysozyme dimer was dose- and time-dependent. The strongest protection was observed after three doses of 20 micrograms/kg administered prior to pharmacological immunosuppression. Reduction in the dose to 2 micrograms/kg and shorter treatment resulted in reduced protective effects. We have also found that the protective action of three doses of lysozyme dimer (2 or 20 micrograms/kg each) administered between cyclophosphamide injection and the antigen, or after antigen administration is weaker than such a treatment prior to cyclophosphamide immunosuppression.

Effect of mechlorethamine on SRBC-induced secondary antibody response in mice.

The effect of low-dose mechlorethamine (5 micrograms/kg) on secondary humoral response to sheep red blood cells (SRBC), depending on time of exposure to the drug in relation to priming and challenge was studied in Balb/c mice. It was found that mechlorethamine in a dose of 5 micrograms/kg stimulated primary humoral response to SRBC resulting in the increased number of the plaque forming cells (PFC) and hemagglutinin titre (19S + 7S). However, this effect waned 10 days after immunization. On the other hand, the same mechlorethamine dose potentiated secondary humoral response to SRBC and increased the number of PFC and anti-SRBC hemagglutinin titres (notably 7S), which was due to the challenging antigenic stimulus. In each immunization, mechlorethamine administration prolonged the potentiating effect of the drug on anti-SRBC hemagglutinin titre. When mechlorethamine was administered to the mice only after priming, the number of PFC increased, but anti-SRBC hemagglutinin titre (7S) remained unchanged. This was likely due to the fact that mechlorethamine administered after priming increases the number of long-lived lymphocytes B, which in turn affect secondary humoral response.