During a mammary immune response, the integrity of the blood-milk barrier is negatively affected and becomes leaky. The aim of the present study was to demonstrate the blood origin, and to investigate changes in the concentration, of various constituents including immunoglobulins in blood and milk during the early phase of lipopolysaccharide (LPS)-induced mastitis. Five lactating dairy cows received continuous β-hydroxybutyrate (BHBA) clamp infusions to maintain elevated BHBA blood concentrations (1.5 to 2.0 mmol/L) from 48 h before and 8 h after LPS administration. One udder quarter was infused with 200 μg of Escherichia coli LPS. A second quarter served as control. Milk and blood samples were taken hourly for 8 h postchallenge (PC). The somatic cell count in LPS-challenged quarters was increased from 4 h PC to the end of the experiment compared with control quarters. In LPS-challenged quarters, l-lactate, BHBA, lactate dehydrogenase (LDH), IgG 1 , and IgG 2 were increased at 3 h PC and remained elevated until the end of experiment (8 h PC) compared with control quarters. In addition, the optical density values in milk in a nonquantitative ELISA for antibodies directed against bluetongue virus (used as a measure of nonspecific antibody transfer; all animals were vaccinated) increased and, thus, indicates an increase in these antibodies in response to LPS treatment. l-Lactate concentration also increased in blood 2 h PC and in the milk of control quarters during the experiment from 3 h PC. A second experiment was conducted in vitro to investigate a possible contribution from destructed milk cells to l-lactate concentration and activity of LDH in milk. Aliquots of milk samples (n = 8) were frozen (−20°C) or disrupted with ultrasound, respectively. Freeze thawing and ultrasound treatment increased LDH in milk samples, but had no effect on l-lactate concentrations. Results suggest that intramammary infusion of LPS induces a systemic response, as evidenced by an elevation of blood l-lactate concentration. The concomitant changes of all investigated components suggest that they were blood derived. However, the increase in blood components in the milk is not necessarily supportive of the mammary immune system, and likely a side effect of reduced blood-milk barrier integrity.

The purpose of our study was to evaluate hematologic acclimatization during 2 weeks of intensive normoxic training with regeneration at moderate altitude (living high-training low, LHTL) and its effects on sea-level performance in well trained athletes compared to another group of equally trained athletes under control conditions (living low - training low, CONTROL). Twenty-one triathletes were ascribed either to LHTL (n = 11; age: 23.0 +/- 4.3 yrs; VO 2 max: 62.5 +/- 9.7 [ml x min -1 x kg -1]) living at 1956 m of altitude or to CONTROL (n = 10; age: 18.7 +/- 5.6 yrs; VO 2 max: 60.5 +/- 6.7 ml x min -1 x kg -1) living at 800 m. Both groups performed an equal training schedule at 800 m. VO 2 max, endurance performance, erythropoietin in serum, hemoglobin mass (Hb tot, CO-rebreathing method) and hematological quantities were measured. A tendency to improved performance in LHTL after the camp was not significant (p < 0.07). Erythropoietin concentration increased temporarily in LHTL (Delta 14.3 +/- 8.7 mU x ml -1; p < 0.012). Hb tot remained unchanged in LHTL whereas was slightly decreased from 12.5 +/- 1.3 to 11.9 +/- 1.3g x kg -1 in CONTROL (p < 0.01). As the reticulocyte number tended to higher values in LHTL than in CONTROL, it seems that a moderate stimulation of erythropoiesis during regeneration at altitude served as a compensation for an exercise-induced destruction of red cells.

We examined two recently described cytokeratin markers, CYFRA 21-1 (cytokeratin fragment recognized by KS 19-1 and BM 19-21 antibodies) and TPS (specific M3 epitope of the tissue polypeptide antigen), in 405 lung cancer patients (91 small-cell and 314 non-small-cell lung cancers) and 59 patients presenting with nonmalignant pulmonary disease. Sensitivity-specificity relationship, as analyzed by receiver operating characteristic curves, demonstrated a higher accuracy of CYFRA 21-1 in comparison with TPS in both small-cell and non-small-cell lung cancers. Thresholds of 3.6 ng/ml and 140 U/L for CYFRA 21-1 and TPS respectively gave a 90% to 95% specificity. Sensitivity of CYFRA 21-1 was the highest in squamous-cell carcinomas (0.61) and the lowest in small-cell lung cancers (0.36), whereas sensitivity of TPS did not vary significantly according to histology (overall sensitivity, 0.40). In non-small-cell lung cancers, both serum CYFRA 21-1 and serum TPS distributions varied significantly according to Mountain's stage of the disease, nodal status, tumor status, and performance status, inasmuch as the worse each above-mentioned variable became, the higher the median and interquartile serum marker level was. Neither CYFRA 21-1 nor TPS was able to accurately discriminate between stage IIIa (marginally resectable) and stage IIIb (unresectable) non-small-cell lung cancers, however. In both small-cell and non-small-cell lung cancers, univariate survival analyses demonstrated that either a CYFRA 21-1 level over 3.6 ng/ml or a TPS level over 140 U/L significantly indicated a poor survival rate. In the whole population, taking into account other significant variables, Cox's model analysis demonstrated that a poor performance index, an advanced stage of the disease, the presence of metastases, elevated serum lactate dehydrogenase, and high serum CYFRA 21-1 (odds ratio, 1.74; 95% confidence interval, [1.33-2.27] were independent prognostic variables. We concluded that CYFRA 21-1 is a significant determinant of survival. Other applications of cytokeratin markers in lung cancer are still limited.

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