ABSTRACT
Two classes of modified analogs of 4-(thiazol-5-yl)benzoic acid-type CK2 inhibitors were designed. The azabenzene analogs, pyridine- and pyridazine-carboxylic acid derivatives, showed potent protein kinase CK2 inhibitory activities [IC50 (CK2α)=0.014-0.017µM; IC50 (CK2α')=0.0046-0.010µM]. Introduction of a 2-halo- or 2-methoxy-benzyloxy group at the 3-position of the benzoic acid moiety maintained the potent CK2 inhibitory activities [IC50 (CK2α)=0.014-0.016µM; IC50 (CK2α')=0.0088-0.014µM] and led to antiproliferative activities [CC50 (A549)=1.5-3.3µM] three to six times higher than those of the parent compound.
Subject(s)
Benzoic Acid/chemistry , Benzoic Acid/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Casein Kinase II/antagonists & inhibitors , Casein Kinase II/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Models, Molecular , Structure-Activity Relationship , Thiazoles/chemistry , Thiazoles/pharmacologyABSTRACT
The aim of this study was to investigate the effect of C-Graft particles on formation of new cementum and bone in periodontal bone defects in dog. Healing and tissue change were histologically determined at 2, 4, 8, and 16 weeks. Little bone or cementum formation was observed in the control group. A statistically significant increase in bone and cementum formation was seen in the C-Graft group compared to the control group (75.4% vs. 44.9%, p < 50.01, 80.4% vs. 46.7%, p < 50.05, respectively). These findings suggest that C-Graft particles provide a scaffold for the regeneration of new bone and cementum.
Subject(s)
Bone Regeneration , Guided Tissue Regeneration, Periodontal , Hydroxyapatites/therapeutic use , Periodontium/injuries , Alkaline Phosphatase/metabolism , Animals , Dental Cementum/pathology , Dogs , Hydroxyapatites/chemistry , Male , Microscopy, Electron, Scanning , Periodontium/pathology , Porosity , Time FactorsABSTRACT
Atypical antipsychotics are rapidly evolving to become the standard pharmacotherapy in schizophrenia; however, the trend of switching to such drugs is not necessarily progressing quickly in East Asia. This might be due to the scarcity of evidence for the efficacy of switching from conventional to atypical antipsychotics, which prompted the authors to examine effects of switching from conventional antipsychotics to an atypical drug, risperidone, in Japanese patients. Fifty patients with chronic schizophrenia completed the study in which combination therapy with other antipsychotics was allowed if monotherapy with risperidone was not tolerated. Symptoms were assessed with the brief psychiatric rating scale (BPRS). Switching to monotherapy was achieved in 34 patients (68%). The number of antipsychotics prescribed to each patient was reduced (from 2.1 to 1.4 drugs; P < 0.001) and the use of antiparkinsonian drugs decreased (P < 0.001). The mean BPRS score was also reduced 6 months after initiation of the switch (P < 0.001). Failure in switching to monotherapy was associated with higher dosage of antipsychotics at baseline. Switching from conventional antipsychotics to risperidone reduced schizophrenia symptoms, antiparkinsonian medication, and polypharmacy. However, a portion of patients, particularly those who receive an excessive dosage of antipsychotics, might not tolerate such switching.
