mobic and Leukocytosis

Non-arteritic anterior ischemic optic neuropathy (NAION) causes a sudden loss of vision and lacks effective treatment. Granulocyte colony-stimulating factor (G-CSF) provides neuroprotection against the experimental optic nerve injuries but also induce leukocytosis upon typical administration. We found synergetic neuroprotective effects of meloxicam and low dose G-CSF without leukocytosis in a rat model of anterior ischemic optic neuropathy (rAION). The WBC counts in the low-dose G-CSF-plus meloxicam-treated group were similar to the sham-operated group. Combination treatment of low-dose G-CSF plus meloxicam preserved RGCs survival and visual function, reduced RGC apoptosis and the macrophages infiltration, and promote more M2 phenotype of macrophage/microglial transition than the low-dose GCSF treatment or the meloxicam treatment. Moreover, the combination treatment induced higher serine/threonine kinase 1 (Akt1) expression. The combination treatment of low-dose G-CSF plus meloxicam lessened the leukocytotic side effect and provided neuroprotective effects via Akt1 activation in the rAION model. This approach provides crucial preclinical information for the development of alternative therapy in AION.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Humans; Leukocyte Count; Leukocytosis; Macrophages; Male; Meloxicam; Neuroprotective Agents; Optic Nerve; Optic Neuropathy, Ischemic; Proto-Oncogene Proteins c-akt; Rats; Retinal Ganglion Cells; Signal Transduction

This work describes recent results from our research program aiming at the synthesis and evaluation of new compounds acting as potential anti-inflammatory drugs. A series of novel acyl-hydrazones bearing 2-aryl-thiazole moiety were synthesized by the condensation between derivatives of 4-[2-(4-methyl-2-phenyl-thiazole-5-yl)-2-oxo-ethoxy]-benzaldehyde and 2, 3 or 4-(2-aryl-thiazol-4-ylmethoxy)-benzaldehyde, respectively and different carboxylic acid hydrazides. The structures of newly synthesized compounds were established by the combined use of IR, (1)H NMR, mass spectral data and elemental analysis. These compounds were tested in vivo for their anti-inflammatory activity, in an acute experimental inflammation. The acute phase bone marrow response, phagocytes' activity and NO synthesis were evaluated. Compounds 10, 15, 17, 18 and 22 reduced the absolute leukocytes count due to the lower neutrophils percentage. Phagocitary index was decreased by all the compounds. Seven of them reduced the phagocitary activity. Five compounds inhibited NO synthesis, 3, 4, 16 and 22 stronger than Meloxicam, the anti-inflammatory reference drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow; Cytokines; Hydrazones; Inflammation; Leukocyte Count; Leukocytes; Leukocytosis; Molecular Structure; Neutrophils; Rats; Stereoisomerism; Thiazoles

Prostaglandins are implicated in periodontal bone destruction. We investigated the effect of a non-selective cyclooxygenase (COX) inhibitor (indomethacin-IND) or a type 2 COX inhibitor (meloxicam-MLX) in an experimental periodontal disease (EPD) model.. Wistar rats were subjected to placement of a nylon thread ligature around the maxillary molars and sacrificed after 7 days. Alveolar bone loss (ABL) was measured in one quadrant as the distance between the cemento-enamel junction and the alveolar bone. The other quadrant was processed for histopathologic analysis. Daily weight and white blood cell count were recorded. Groups were treated subcutaneously for 7 days with either IND (0.5, 1, or 2 mg/kg) or MLX (0.75, 1.5, or 3 mg/kg). Controls received no treatment. Macroscopic analysis of the gastric mucosa was done. The control group did not receive any manipulation, and a non-treated group consisted of rats subjected to periodontitis that received no pharmacological treatment.. In the non-treated (NT) group, there was significant ABL, severe mononuclear influx, and an increase in osteoclast numbers. Significant neutrophilia and lymphomonocytosis occurred at 6 hours and at 7 days, respectively, as compared to controls. Significant weight loss persisted until the seventh day in the NT group. Both IND and MLX reduced ABL and histopathologic changes. Neutrophilia and lymphomonocytosis were also significantly reversed. Both IND and MLX induced earlier weight recovery. The stomachs of the IND (1 and 2 mg/kg) groups presented hemorrhage and ulcers, whereas in the MLX-treated groups, there were mild petechiae just in the 3 mg/kg group.. COX inhibition prevented ABL in this experimental periodontal disease model. MLX displays similar efficacy and less gastric damage than IND. MLX may provide a better risk/benefit ratio in the treatment of human periodontitis than non-selective COX inhibitors.

Topics: Alveolar Bone Loss; Alveolar Process; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cell Count; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Disease Models, Animal; Indomethacin; Injections, Subcutaneous; Isoenzymes; Leukocyte Count; Leukocytes, Mononuclear; Leukocytosis; Male; Meloxicam; Molar; Neutrophils; Osteoclasts; Periodontitis; Peroxidases; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Stomach; Thiazines; Thiazoles; Tooth Cervix