Effect of Antibiotics on Polymorphonuclear Leukocyte Functions and Myeloperoxidase Activity, Glutathione and Malondialdehyde Levels in Allergic Asthma.

We investigated the effect of ciprofloxacin, rifampicine and doxycycline on myeloperoxidase (MPO) activity, glutathione (GSH) and malondialdehyde (MDA) levels in allergic asthma patients and healthy volunteers. Polymorphonuclear leukocytes (PMNs) were isolated with ficoll-hypaque gradient centrifugation method. MPO activity was assayed with modified o-dianisidine, GSH by Ellman's and MDA levels by Beuge's method. PMN functions and MDA levels of patients significantly decreased when compared with healthy volunteers. Ciprofloxacin significantly increased PMN functions, MPO activity and MDA levels of both groups. We have demonstrated that ciprofloxacin has beneficial effects on MPO activity and PMN functions in allergic asthma patients and healthy volunteers.

Potential adjuvant effects of Nigella sativa seeds to improve specific immunotherapy in allergic rhinitis patients.

OBJECTIVE: To investigate the effects of Nigella sativa seed supplementation on symptom levels, polymorphonuclear leukocyte (PMN) functions, lymphocyte subsets and hematological parameters of allergic rhinitis. SUBJECTS AND METHODS: Twenty-four patients randomly selected from an experimental group of 31 (mean age 34 years) sensitive to house dust mites with allergic rhinitis and a control group of 8 healthy volunteers (mean age 23 years) were treated with allergen-specific immunotherapy in conventional doses for 30 days. After a month of immunotherapy, 12 of the 24 patients and the 8 healthy volunteers were given N. sativa seed supplementation (2 g/day orally) for 30 days. The remaining 12 patients continued only on immunotherapy during the same period. The other 7 patients were given 0.1 ml saline solution subcutaneously once a week as a placebo. The symptom scores, PMN functions, lymphocyte subsets and other hematological parameters were evaluated before and after all treatment periods. RESULTS: There was a statistically significant increase in the phagocytic and intracellular killing activities of PMNs of patients receiving specific immunotherapy, especially after the addition of N. sativa seed. The CD8 counts of patients receiving specific immunotherapy plus N. sativa seed supplementation significantly increased compared to patients receiving only specific immunotherapy. PMN functions of healthy volunteers significantly increased after N. sativa seed supplementation compared to baseline. CONCLUSION: N. sativa seed supplementation during specific immunotherapy of allergic rhinitis may be considered a potential adjuvant therapy.

Colonic delivery of compression coated nisin tablets using pectin/HPMC polymer mixture.

Nisin containing pectin/HPMC compression coated tablets were prepared and their in vitro behavior tested for colonic delivery. Nisin is a 34-amino-acid residue long, heat stable peptide belonging to the group A lantibiotics with wide antimicrobial activity against Gram-positive bacteria. The invention can be useful for treating colonic infectious diseases such as by Clostridium difficile, and also by colonization of vancomycin-resistant enterococci. In this study, each 100mg core tablet of nisin was compression coated with 100% pectin, 90% pectin-10% HPMC, 85% pectin-15% HPMC, 80% pectin-20% HPMC, 75% pectin-25% HPMC, 100% HPMC at a coat weight of 400mg. The concentration and the activity of nisin were quantified using Well Diffusion Agar Assay. Drug release studies were carried out in pH 3.3 buffer solution. System degradation/erosion experiments were carried out in pH 1.2, 3.3, and 6.8 buffers using a pectinolytic enzyme. The biological activity and NMR studies were performed to assess the stability of nisin during the processing and after the in vitro tests. It was found that pectin alone was not sufficient to protect the nisin containing core tablets. At the end of the 6h 40% degradation was observed for 100% pectin tablets. HPMC addition required to control the solubility of pectin, a 5% increase in HPMC ratio in pectin/HPMC mixture provided a 2-h lag time for nisin release. Eighty percent pectin-20% HPMC appeared to be an optimum combination for further evaluation. Tablets maintained their integrity during the 6-h dissolution test, approximating the colon arrival times. Nisin was found to be active/stable during processing and after in vitro tests. Effect of polymer hydration on pectin degradation was found to be crucial for the enzyme activity. Sufficiently hydrated pectin degraded faster. The pectin/HPMC envelope was found to be a good delivery system for nisin to be delivered to the colon.

The effects of some antibiotics on polymorphonuclear leukocyte functions of elderly patients in vitro before and after zinc supplementation.

The effects of ciprofloxacin, cefodizime, rifampicine, doxycycline and cefodizime + rifampicine combination on polymorphonuclear leukocyte (PMN) functions (phagocytosis and intracellular killing activity) were investigated in vitro in elderly patients and compared with those of healthy young volunteers before and after zinc supplementation. PMNs of 13 elderly hypertensive patients and 10 healthy young volunteers were isolated by Ficoll-Hypaque gradient centrifugation method from venous blood with EDTA. The subjects were given 22 mg/daily/oral zinc supplementation for 1 month. Serum zinc levels before and after supplementation were measured by flame atomic absorbtion spectrophotometer and the effects of each drug on PMN functions at therapeutic concentrations were investigated. Ciprofloxacin significantly increased the PMN's phagocytic activity of elderly patients (p = 0.002) before zinc supplementation and significantly increased both PMN functions of elderly patients (p = 0.002) after zinc supplementation. The same antibiotic significantly increased both PMN functions of healthy young volunteers (p = 0.005 and p<0.05, respectively) before and after zinc supplementation when compared with the control (drug-free). Cefodizime significantly increased the PMN's phagocytic activity of elderly patients (p = 0.003, p = 0.002) before and after zinc supplementation when compared with the control (drug-free). It also significantly increased both PMN functions of healthy young volunteers (p = 0.005 and p<0.05, respectively) before and after zinc supplementation when compared with the control (drug-free). Doxycycline significantly increased PMN's intracellular killing activity of healthy young volunteers before zinc supplementation (p<0.05) when compared with the control (drug-free) values. Rifampicine significantly decreased PMN's phagocytic activity of elderly patients (p<0.05) after zinc supplementation. Cefodizime+rifampicine combination significantly increased PMN's phagocytic activity at therapeutic concentrations of healthy young volunteers (p = 0.005) before zinc supplementation and PMN's phagocytic activity of elderly patients (p<0.05) after zinc supplementation when compared with the control (drug-free). Consequently, in the present study from the antibiotics ciprofloxacin, cefodizime and cefodizime + rifampicine combination, which are accepted as biological response modifiers have demonstrated stimulatory effects by significantly increasing polymorphonuclear leucocyte functions (phagocytosis and/or intracellular killing activity) of elderly patients and healthy young volunteers in vitro before and after zinc supplementation. Additionally zinc supplementation has more immunostimulatory effects on PMN functions of healthy young volunteers than elderly patients.

Effect of antituberculous drugs on human polymorphonuclear leukocyte functions in vitro.

The aim of the study was to investigate antituberculous drugs effects on polymorphonuclear leukocyte (PMN) functions (phagocytic activity and intracellular killing activity) in vitro. PMNs obtained from healthy volunteers were incubated with antituberculous drugs (isoniazid [INH], rifampin [RIF], pyrazinamide [PZA], ethambutol [EMB], streptomycin [S], amikacin [A], ofloxacin [OFLX], prothionamide [PTH] and cycloserine [CyC]) and different combinations at therapeutic serum concentrations. Phagocytic activity of PMNs was significantly increased when compared with controls by PTH (p<0.001), A (p<0.001), OFLX (p<0.001), INH+RIF+S combination (p<0.01), A+OFLX combination (p<0.05), A+OFLX+CyC combination (p<0.01) and A+OFLX+CyC+PTH+EMB combination (p<0.01). Intracellular killing activity of PMNs was significantly increased by OFLX when compared with the control (p<0.05). No significant difference was observed in functions of PMN for other drugs when compared with control (p>0.05). Functions of PMN were significantly increased by OFLX when compared with A+OFLX combination (p<0.05). Phagocytic activity of PMNs was significantly increased by A+OFLX+CyC combination and A+OFLX+CyC+PTH+EMB combination when compared with A+OFLX+CyC+PTH combination and A+OFLX+CyC+PTH+PZA combination (p<0.05). No significant difference was found in functions of PMN between the other groups (p>0.05). In conclusion, some antituberculous drugs alone or in combination enhanced PMN functions, although in combination no additive or synergistic effects were detected. Moreover, none of the antituberculous drugs alone or in combination significantly decreased PMN functions. The drugs having adverse effects on immune functions would better be replaced with equally effective drugs or drug combinations having positive effects on PMN functions.

Effect of montelukast on polymorphonuclear leukocyte functions in asthmatic patients.

Leukotriene receptor antagonists are being used widely in the treatment of bronchial asthma. They have been shown to possess anti-inflammatory properties, but there is no sufficient data about their effects on polymorphonuclear leukocyte functions. The aim of this study was to investigate the effects of montelukast, a specific cysteinyl leukotriene-1 receptor antagonist, on human polymorphonuclear leukocyte (PMN) functions (phagocytic and intracellular killing activity) in asthmatic patients. Fifteen mild to moderate asthmatic patients were included in the study. They were treated with montelukast (10 mg/day per os) in addition to their previous medications for 2 weeks. Whole blood samples of patients were taken before and after this treatment period. Phagocytic activities and intracellular killing activities of polymorphonuclear leukocytes isolated from whole blood samples were tested by using appropriate technics. Phagocytic and intracellular killing activities of PMNs were significantly increased (p<0.001, p<0.05) by montelukast compared to those before treatment. These results show that montelukast has an enhancing effect on PMN functions in asthmatic patients.

Effect of antipyretics on polymorphonuclear leukocyte functions in children.

The aim of this study was to investigate whether fever and antipyretic drugs had an adverse effect on human polymorphonuclear leukocyte (PMN) functions (phagocytic and intracellular killing activity). Twenty febrile children with an axillary temperature of 39-40 degrees C and 20 healthy children without fever were included. Polymorphonuclear leukocytes were isolated. The effects of in vitro addition of antipyretic drugs (acetaminophen, metamizole sodium, nimesulid and ibuprofen) on PMN functions were tested. Phagocytic activity was assayed by the ingestion of yeast cells by PMNs and intracellular killing activity by the ingestion of yeast cells (stained blue) killed by PMNs. PMNs derived from febrile children exhibited better phagocytic activity when ibuprofen was added. In contrast, phagocytic activity was enhanced when acetaminophen, metamizole sodium or nimesulid was added in children without fever. Intracellular killing activity was enhanced when ibuprofen or metamizole sodium was added in children without fever. We conclude the antipyretic drugs at safely achievable concentrations do not suppress PMN function in vitro.