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Research paper thumbnail of Clindamycin and tetracycline as immunomodulating agents: an in vivo study

Drugs under experimental and clinical research

The present study was undertaken to determine the effects of clindamycin and tetracycline, both i... more The present study was undertaken to determine the effects of clindamycin and tetracycline, both intravenously administered, on antibody response to thymus-dependent antigen (PC-KLH) in BALB/c mice. The immunological parameters evaluated were: DPFC/spleen (direct plaque forming-cells), antibody secretion median rate (PC50), heterogeneity index (Hi), number of total splenic lymphocytes and cellular viability. The results showed that clindamycin (i.v.) increased the humoral response; 28 mg/kg was the dose that showed the greatest enhancement (+73%). The PC50 was not affected by clindamycin but Hi decreased at 28 mg/kg and increased at 2.8 mg/kg doses, although neither result was statistically significant. When tetracycline was given i.v., a slight decrease in the anti-PC DPFC number was observed. Although the PC50 was greater at 10 mg/kg (p less than 0.05), Hi was smaller at the 1 mg/kg dose (p less than 0.05).

Research paper thumbnail of Effect of cefotaxime on antibody-producing cells of mouse spleen

Journal of chemotherapy (Florence, Italy)

Research paper thumbnail of Comparative effects of three beta-lactam antibiotics on anti-PC direct plaque-forming cells

Drugs under experimental and clinical research

Penicillin G, cefotaxime and clavulanic acid administered intravenously were studied for their im... more Penicillin G, cefotaxime and clavulanic acid administered intravenously were studied for their immunomodulating properties. BALBC/c mice were immunized using PC-KLH as thymus-dependent antigen at the same time as the antibiotic was injected. The effect on antibody response was evaluated 5 days after immunization. Critical immunological parameters such as direct antibody-producing cells, Ab-secretion median rate, secretion rate heterogeneity and cellular viability, were studied. The most stimulatory effects were with penicillin G at the 4 x 10(6) IU/kg dose (+73%), cefotaxime at the 366 mg/kg dose (+80%) and clavulanic acid at 1 mg/kg (+218%). The experiments using inhibition of plaque formation with free hapten demonstrate that all the drugs studied decreased the antibody secretion rate and this parameter appeared more heterogeneous when cefotaxime and clavulanic acid were given; however, with penicillin this parameter was more heterogeneous at 2 x 10(5) mg/kg and 1 x 10(3) IU/kg respectively. When clavulanic acid was injected, the number of lymphocytes per spleen, size and friability of the spleen were increased versus the control mice. The present data show that all of the drugs studied present immunostimulating effects on humoral response, against thymus-dependent antigen, but have differently pronounced enhancements.

Research paper thumbnail of Serum-independent binding of lipopolysaccharide to human monocytes is trypsin sensitive and does not involve CD14

Immunology, 1993

The nature of the binding sites for lipopolysaccharide (LPS) on human monocytes was investigated ... more The nature of the binding sites for lipopolysaccharide (LPS) on human monocytes was investigated using fluorescein isothiocyanate (FITC)-labelled LPS from Salmonella minnesota R595 (ReLPS). In the absence of serum, ReLPS bound to monocytes and this interaction was trypsin sensitive. A concentration of 0.1 mg/ml resulted in a 90% loss of LPS binding, while low concentrations increased this binding. Trypsin-treated monocytes recovered FITC-ReLPS binding after 20 hr culture, which was abrogated in the presence of cycloheximide and actinomycin D. This showed that de novo protein and mRNA synthesis were essential. A number of different proteins have been implicated in cellular binding of LPS to monocytes. In this paper we show that CD14 is not involved in direct binding of FITC-ReLPS to monocytes, since anti-CD14 monoclonal antibody (mAb) (3C10) and removal of most of cell-surface CD14 by phosphatidylinositol-specific phospholipase C did not prevent FITC-ReLPS binding. Furthermore, LPS a...

Research paper thumbnail of Influence of lomefloxacin on phagocytosis and killing activity of macrophagcs and neutrophils

Journal of Antimicrobial Chemotherapy, 1992

Research paper thumbnail of Immunomodulatory effect of cefminox

Journal of Antimicrobial Chemotherapy, 1994

Research paper thumbnail of Risk of thromboembolism with thrombopoietin receptor agonists in adult patients with thrombocytopenia: systematic review and meta-analysis of randomized controlled trials

Medicina Clínica, 2012

Background and objective: Thrombopoietin receptor (TPOr) agonists (romiplostim and eltrombopag) a... more Background and objective: Thrombopoietin receptor (TPOr) agonists (romiplostim and eltrombopag) are a new approach for the treatment of thrombocytopenia-associated conditions. They promote megakaryocyte differentiation, proliferation and platelet production. In the European Union, both are orphan drugs with an indication restricted to splenectomized immune thrombocytopenic purpura patients who are refractory to other treatments. Due to increasing platelet counts, these drugs may represent a risk for thromboembolic complications. We analyzed whether TPOr agonists affect thromboembolisms occurrence in adult thrombocytopenic patients. Materials and methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Searches were carried out in PubMed, SCOPUS, Cochrane Central Register, regulatory agencies websites and publicly available registries of manufacturers. RCTs using romiplostim or eltrombopag in at least one group were included. Absolute risk ratios (ARR), number needed to harm (NNH) and relative risks (RR) were provided. Heterogeneity was analyzed using Cochran's Q test and I 2 statistic. Results: Of 373 publications identified, 8 studies met the inclusion criteria (n = 1180 patients). The quality of reporting amongst studies was variable. Estimated frequency of thromboembolisms was 3.1% (95% CI, 1.8-4.4%) for TPOr agonists and 1.7% (95% CI, 0.3-3.1%) for controls. Summary analyses produced overall meta-ARR for thromboembolisms of 1.8% (95% CI, À0.1-3.6%), and meta-RR of 1.5 (95% CI, 0.7-3.3), meaning a NNH of 55 (1 additional thromboembolism for each 55 patients treated with TPOr agonists). All pooled estimates were homogeneous. Conclusions: TPOr agonists show a numerically but non-statistically significant trend to increase the occurrence of thromboembolisms compared to controls, but analyses were underpowered and in some studies information on outcomes was incomplete and of poor quality.

Research paper thumbnail of Clindamycin and tetracycline as immunomodulating agents: an in vivo study

Drugs under experimental and clinical research

The present study was undertaken to determine the effects of clindamycin and tetracycline, both i... more The present study was undertaken to determine the effects of clindamycin and tetracycline, both intravenously administered, on antibody response to thymus-dependent antigen (PC-KLH) in BALB/c mice. The immunological parameters evaluated were: DPFC/spleen (direct plaque forming-cells), antibody secretion median rate (PC50), heterogeneity index (Hi), number of total splenic lymphocytes and cellular viability. The results showed that clindamycin (i.v.) increased the humoral response; 28 mg/kg was the dose that showed the greatest enhancement (+73%). The PC50 was not affected by clindamycin but Hi decreased at 28 mg/kg and increased at 2.8 mg/kg doses, although neither result was statistically significant. When tetracycline was given i.v., a slight decrease in the anti-PC DPFC number was observed. Although the PC50 was greater at 10 mg/kg (p less than 0.05), Hi was smaller at the 1 mg/kg dose (p less than 0.05).

Research paper thumbnail of Effect of cefotaxime on antibody-producing cells of mouse spleen

Journal of chemotherapy (Florence, Italy)

Research paper thumbnail of Comparative effects of three beta-lactam antibiotics on anti-PC direct plaque-forming cells

Drugs under experimental and clinical research

Penicillin G, cefotaxime and clavulanic acid administered intravenously were studied for their im... more Penicillin G, cefotaxime and clavulanic acid administered intravenously were studied for their immunomodulating properties. BALBC/c mice were immunized using PC-KLH as thymus-dependent antigen at the same time as the antibiotic was injected. The effect on antibody response was evaluated 5 days after immunization. Critical immunological parameters such as direct antibody-producing cells, Ab-secretion median rate, secretion rate heterogeneity and cellular viability, were studied. The most stimulatory effects were with penicillin G at the 4 x 10(6) IU/kg dose (+73%), cefotaxime at the 366 mg/kg dose (+80%) and clavulanic acid at 1 mg/kg (+218%). The experiments using inhibition of plaque formation with free hapten demonstrate that all the drugs studied decreased the antibody secretion rate and this parameter appeared more heterogeneous when cefotaxime and clavulanic acid were given; however, with penicillin this parameter was more heterogeneous at 2 x 10(5) mg/kg and 1 x 10(3) IU/kg respectively. When clavulanic acid was injected, the number of lymphocytes per spleen, size and friability of the spleen were increased versus the control mice. The present data show that all of the drugs studied present immunostimulating effects on humoral response, against thymus-dependent antigen, but have differently pronounced enhancements.

Research paper thumbnail of Serum-independent binding of lipopolysaccharide to human monocytes is trypsin sensitive and does not involve CD14

Immunology, 1993

The nature of the binding sites for lipopolysaccharide (LPS) on human monocytes was investigated ... more The nature of the binding sites for lipopolysaccharide (LPS) on human monocytes was investigated using fluorescein isothiocyanate (FITC)-labelled LPS from Salmonella minnesota R595 (ReLPS). In the absence of serum, ReLPS bound to monocytes and this interaction was trypsin sensitive. A concentration of 0.1 mg/ml resulted in a 90% loss of LPS binding, while low concentrations increased this binding. Trypsin-treated monocytes recovered FITC-ReLPS binding after 20 hr culture, which was abrogated in the presence of cycloheximide and actinomycin D. This showed that de novo protein and mRNA synthesis were essential. A number of different proteins have been implicated in cellular binding of LPS to monocytes. In this paper we show that CD14 is not involved in direct binding of FITC-ReLPS to monocytes, since anti-CD14 monoclonal antibody (mAb) (3C10) and removal of most of cell-surface CD14 by phosphatidylinositol-specific phospholipase C did not prevent FITC-ReLPS binding. Furthermore, LPS a...

Research paper thumbnail of Influence of lomefloxacin on phagocytosis and killing activity of macrophagcs and neutrophils

Journal of Antimicrobial Chemotherapy, 1992

Research paper thumbnail of Immunomodulatory effect of cefminox

Journal of Antimicrobial Chemotherapy, 1994

Research paper thumbnail of Risk of thromboembolism with thrombopoietin receptor agonists in adult patients with thrombocytopenia: systematic review and meta-analysis of randomized controlled trials

Medicina Clínica, 2012

Background and objective: Thrombopoietin receptor (TPOr) agonists (romiplostim and eltrombopag) a... more Background and objective: Thrombopoietin receptor (TPOr) agonists (romiplostim and eltrombopag) are a new approach for the treatment of thrombocytopenia-associated conditions. They promote megakaryocyte differentiation, proliferation and platelet production. In the European Union, both are orphan drugs with an indication restricted to splenectomized immune thrombocytopenic purpura patients who are refractory to other treatments. Due to increasing platelet counts, these drugs may represent a risk for thromboembolic complications. We analyzed whether TPOr agonists affect thromboembolisms occurrence in adult thrombocytopenic patients. Materials and methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Searches were carried out in PubMed, SCOPUS, Cochrane Central Register, regulatory agencies websites and publicly available registries of manufacturers. RCTs using romiplostim or eltrombopag in at least one group were included. Absolute risk ratios (ARR), number needed to harm (NNH) and relative risks (RR) were provided. Heterogeneity was analyzed using Cochran's Q test and I 2 statistic. Results: Of 373 publications identified, 8 studies met the inclusion criteria (n = 1180 patients). The quality of reporting amongst studies was variable. Estimated frequency of thromboembolisms was 3.1% (95% CI, 1.8-4.4%) for TPOr agonists and 1.7% (95% CI, 0.3-3.1%) for controls. Summary analyses produced overall meta-ARR for thromboembolisms of 1.8% (95% CI, À0.1-3.6%), and meta-RR of 1.5 (95% CI, 0.7-3.3), meaning a NNH of 55 (1 additional thromboembolism for each 55 patients treated with TPOr agonists). All pooled estimates were homogeneous. Conclusions: TPOr agonists show a numerically but non-statistically significant trend to increase the occurrence of thromboembolisms compared to controls, but analyses were underpowered and in some studies information on outcomes was incomplete and of poor quality.