A comparative study of the effects of meloxicam and flunixin meglumine (NSAIDs) as adjunctive therapy on interferon and tumor necrosis factor production in calves suffering from enzootic bronchopneumonia.

The study was performed on 18 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided into three groups and respectively treated with oxytetracycline and meloxicam--Group I (9 animals); oxytetracycline and flunixin meglumine--Group II (3 animals); and oxytetracycline only--Group III (6 animals--control). The following observations were recorded before treatment (1st day) and two days later (3rd day): body temperature, the serum level of interferon (IFN) and tumor necrosis factor (TNF) as well as cytokine production by bronchoalveolar lavage (BAL) cells. The treatment of calves with a combination of oxytetracycline and meloxicam (Group I) and especially with oxytetracycline and flunixin meglumine (Group II) caused a significantly faster, in comparison to the control group, normalization of body temperature. Both drugs, meloxicam and especially flunixin meglumine, inhibited excessive TNF production in the organism (measured as the serum level of cytokine). Moreover, BAL cells isolated from calves treated with both NSAIDs were still able, ex vivo, to release TNF, in contrast to the control group (treated only with tetracycline) which lost the ability to produce TNF. The treatment of the calves with meloxicam and flunixin meglumine did not significantly influence the levels of IFN in sera but normalized ex vivo IFN production in BAL cells. These results suggest that the combination of meloxicam with an antibiotic or flunixin meglumine with an antibiotic which does not exert an immunosuppressive influence on the organism of calves suffering from enzootic bronchopneumonia is equally effective in the treatment of calves and superior to the antibiotic alone.

Spinal fusion for lumbar instability: does it have a scientific basis?

The validity of spinal fusion for lumbar instability is considered. Some difficulty lies in the interpretation of the term instability. The differing interpretations in the clinical, radiologic, and biomechanical contexts are discussed. These interpretations may only be reconciled if the confusion between hypermobility and instability is removed and some recourse is made to soft tissue integrity. Fusion is considered in the context of the functioning spine as a whole. Although the aim of the surgery is usually to produce a solid arthrodesis, some studies show that this can compromise the functioning of the rest of the spine. Furthermore, there is some evidence that pseudarthrosis itself may not be detrimental. Dynamic imaging offers the potential for improved diagnosis and assessment, but further work is needed to pave the way for better selection criteria and treatment strategies.

Methanol adduct of puupehenone, a biologically active derivative from the marine sponge Hyrtios species.

A methanol adduct of puupehenone (1), 15alpha-methoxypuupehenol (2), an artifact resulting from the action of MeOH on puupehenone, was isolated during purification of the CH(2)Cl(2) extract of the New Caledonian marine sponge Hyrtios sp., as the major constituent. Its chemical structure was elucidated by 2D NMR experiments. Compound 2 displayed similar antimicrobial and antifungal activity as puupehenone and a lower cytotoxic activity toward KB cells with ED(50) values of 6 and 0.5 microg/mL, respectively. Compound 2 was slightly more active against three strains of Plasmodium falciparum than puupehenone.

The effect of steroidal and non-steroidal anti-inflammatory drugs on the cellular immunity of calves with experimentally-induced local lung inflammation.

We examined the effect of a single intravenous dose of flumetasone (SAID) and meloxicam (NSAID) treatment of calves with experimentally-induced localized lung inflammation on immunological and hematological variables such as total protein, gamma globulin, hemoglobin (Hb) concentrations, alkaline phosphatase activity, packed red cell volume (PCV), red blood cell (RBC) and white blood cell (WBC) counts. The influence of drug treatment on the phagocytic activity of WBC and bronchoalveolar lavage (BAL) cells and their ex vivo ability to produce interferon (IFN) and tumor necrosis factor (TNF) after induction with Newcastle disease virus (NDV), as well as on the development of PHA-induced skin delayed hypersensitivity reaction was also determined. Two days after the treatment of calves with experimentally-induced local lung inflammation with flumetasone (5 mg per calf), we observed a significant increase in WBC count, especially neutrophils, and a decrease in gamma globulin concentration, in the percent of blood phagocytic cells and their random migration. Flumetasone treatment also inhibited the development of skin delayed hypersensitivity reaction. In contrast, the treatment of calves with meloxicam (50 mg per calf) did not influence any hematological parameters or skin reactivity. Both drugs, flumetasone and meloxicam, influenced TNF production in ex vivo cultures of blood and BAL cells, inhibiting excessive TNF production induced by local lung inflammation. Contrary to TNF, the treatment of calves with meloxicam and flumetasone enhanced ex vivo IFN production in blood and BAL cells. Histological examination of lung tissue revealed that in control calves (those not treated with anti-inflammatory drugs) and in calves treated with flumetasone, symptoms of stromo-purulent inflammation of pulmonary tissue developed. However, in calves treated with meloxicam, only interstitial inflammation with a slight thickening of interalveolar septa and infiltration of lymphoid cells was observed. These results suggest that in this model of pneumonia, it is more appropriate to use a single dose of meloxicam, rather than flumetasone, to modulate lung inflammation.

Tumor necrosis factor and interferon activity in the circulation of calves after repeated injection of low doses of lipopolysaccharide.

The effect of two intravenous (i.v.) injections of low doses of lipopolysaccharide (LPS)(0.1 microgram/kg of body weight) administered at 7-day intervals on the systemic release of tumor necrosis factor (TNF) and interferon (IFN), on the rectal temperature, breathing and heart rate, and on packed cell volume (PCV), plasma glucose concentration, white blood cell (WBC) counts in 3-week-old calves, was estimated. The first injection of LPS caused a significant increase in breathing and heart rate, rectal temperature, prolonged hypoglycemia and leukopenia, but no significant changes in PCV were observed. TNF and IFN activity peaked at 2 h after LPS injection and disappeared from circulation by 4 h and 5 h, respectively. After the second injection of LPS, the reaction of calves was similar to that observed after the first injection, however, the breathing rate and TNF systemic production were significantly reduced. The results obtained indicate that a low dose of LPS leads to the development of 'late' tolerance manifested by hyporeactivity to TNF production but with maintained responsivity to IFN production, pyrogenic, hypoglycemic and leukemic response to the second injection of LPS. In conclusion, these results demonstrate that the tolerance response is not universal to all hematologic and immunologic parameters, and that the response needs to be evaluated with respect to the specific variable.

Alterations in peripheral blood leukocytes functions during enzootic bronchopneumonia of calves. Effect of treatment with antibiotics and immunomodulators.

Twelve calves from over veal calf farm were divided into two groups: group I-6 calves which developed typical signs of enzootic bronchopneumonia and group II-6 calves with no symptoms of the disease. Both groups of calves were compared with respect to changes in several hematological parameters. Some functions of peripheral blood leukocytes as random migration, phagocytic index, percent of phagocytic cells and percent of NBT positive cells were also scored. In addition, changes in serum levels of interferon (IFN) and tumor necrosis factor (TNF) and the ability of peripheral blood leukocytes (PBL) to produce IFN and TNF were quantitated by biological methods. On the day of diagnosis, in group I of calves a significant increase in the total serum protein concentration, hemoglobin content, red and white blood cells counts in comparison to control calves (group II) was observed. The increased number of NBT positive neutrophils and moderate levels of serum IFN and TNF correlated with elevated body temperature, breathing and heart rates. Calves with bronchopneumonia (group I) after diagnosis of the disease were treated with Tylbian (tylosine derivative), Flumetazon (glucocorticoid), Emulselvet (immunomodulator), bromhexinum and sulphonamides. Seven days after the beginning of treatment with medicaments a significant improvement in clinical symptoms was observed, however, the ability of PBL to cytokine production increased significantly 2 weeks after beginning of treatment and correlated with significant increase in random migration of neutrophils and their phagocytic activity, measured by the percent of phagocytic cells. Unexpectedly, in control calves (group II), not exhibiting any symptoms of bronchopneumonia at the beginning of experiment, high serum IFN titers were detected which decreased significantly during the first week of observation. In contrast to that the ability of PBL of control calves to produce IFN increased significantly within 3 weeks of observation. The correlations between the ability of PBL to produce cytokine and the development of clinical symptoms of bronchopneumonia are discussed.

Interferon and tumor necrosis factor production during endotoxemia in sheep.

In humans endotoxemia has often been associated with the development of adult respiratory distress syndrome (ARDS). Sheep have an abundant population of pulmonary intravascular macrophages, therefore they are a popular animal model for ARDS. In this study we characterized the temporal sequence and duration of the release of two cytokines: tumor necrosis factor (TNF) and interferon (IFN) and evaluated the effect of lipopolysaccharide (LPS) dose. Rectal temperature and white blood cell (WBC) count were also measured. Twenty four adult sheep were given E. coli endotoxin at a dose of 0 (saline solution) 0.05, 0.1 and 1.0 microg/kg of body weight by intravenous (i.v.) bolus. In all groups, TNF-alpha was produced earlier (3-4.5 h) after injection than IFN (4-5 h). No correlation between increased rectal temperature, the magnitude of leukopenia and time course of both cytokines production was observed. No straight relationship between LPS dose and the titer of cytokines was seen, but lower doses of LPS-induced delayed cytokine response in comparison to the dose 1 microg/kg of LPS. As IFN, present in the circulation of sheep, was mainly alpha/beta type, the role of this class of IFN in endotoxemia is discussed.

[The effect of zinc on mineral, hematological and immunological indices in calves]. / Wplyw cynku na wskazniki mineralne, hematologiczne i odpornosciowe cielat.

The aim of this work was to study the effect of zinc added to feed on some selected biochemical and haematological indices and its stimulatory action on immunity of calves during its physiological decrease. Investigations were carried out on 18 calves aged 20 days. Twelve calves were divided into 2 groups and they received 450 and 900 mg of Zn++ under the form of ZnSO4 x 7H2O. The following parameters were examined: serum and tissue concentrations of Zn, Cu, Fe and Ca, number of erythrocytes and leucocytes, Hb and Ht indices, leukogram with shifting blood picture to the left, percentage of NBT-positive neutrophils, ability of macrophages for spontaneous migration and serum carotene, vitamin A and gamma-globulin levels. Increased serum and liver zinc levels were found in experimental animals in comparison with a control group and the ability of macrophages for spontaneous migration was increased. Index of shifting the white blood cells to young forms and the percentage of NBT-positive neutrophils were variable. A significant increase in carotene, vitamin A and gamma-globulin levels was also observed.

Sesquiterpene quinones as immunomodulating agents.

The influence of sesquiterpene quinones and of a sesquiterpene hydroquinone, isolated from the sponge Smenospongia sp. on normal and tumour cells, was investigated. Most showed cytotoxic effects on L1210 leukemia cells. However, their activity on normal cells, such as murine spleen lymphocytes and human peripheral lymphocytes, revealed different behaviours: some of them inhibited, while other enhanced mitogen-stimulated lymphocyte proliferation. These biological studies revealed products modulating immune responses.