The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis

Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).

Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.

Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?r²: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.

Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD.     

Can muscle weakness and disability influence the relationship between pain catastrophizing and pain worsening in patients with knee osteoarthritis? A cross-sectional study

ObjectiveTo verify if the relationship between pain catastrophizing and pain worsening would be mediated by muscle weakness and disability in patients with symptomatic knee osteoarthritis.MethodsThis was a cross-sectional study in a hospital out-patient setting. Convenience sampling was used with a total of 50 participants with symptomatic knee osteoarthritis. Pain and the activities of daily livings (ADL) were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale. Pain catastrophizing was assessed using the Coping Strategy Questionnaire (CSQ) subscale. Muscle strength of knee extension and 30-s chair stand test (30CST) were also assessed. Path analysis was performed to test the hypothetical model. Goodness of fit of models were assessed by using statistical parameters such as the chi-square value, goodness of fit index (GFI), adjusted goodness of fit index (AGFI), comparative fit index (CFI), and root mean square error of approximation (RMSEA).ResultsThe chi-square values were not significant (chi-square = 0.283, p = 0.594), and the indices of goodness of fit were high, implying a valid model (GFI = 1.000; AGFI = 0.997; CFI = 1.000; RMSEA = 0.000). Pain was influenced significantly by muscle strength and ADL; muscle strength was influenced significantly by ADL via 30CST; ADL was influenced by pain catastrophizing.ConclusionThe relationship between pain catastrophizing with pain worsening are mediated by muscle weakness and disability.     

Lesion regression rate based on RECIST: prediction of treatment outcome in patients with head and neck cancer treated with chemoradiotherapy compared with FDG PET-CT

The aim of this study was to evaluate whether the lesion regression rate (ΔLR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria could be used for the prediction of treatment outcome in head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiotherapy (CRT) compared with FDG PET-CT. A total of 33 patients underwent MRI and PET-CT at pretreatment and at 8 weeks after CRT. We assessed the treatment outcome by analyzing the following parameters: the RECIST criteria, ΔLR, the European Organization for Research and Treatment of Cancer (EORTC) criteria, and pretreatment SUV_max of the primary tumor and node. The correlation between the analysis of the parameters and the results of the long-term follow-up of the patients was determined. The RECIST did not significantly correlate with locoregional control (LRC) or survival. The ΔLR was significantly lower for the lesions with locoregional failure (LRF) than for those with LRC. A threshold ΔLR of 48% revealed a sensitivity of 72.7% and specificity of 77.3% for the prediction of LRF. Progression-free survival (PFS) of patients with ΔLR ≥ 48% was significantly better than that of patients with ΔLR < 48% (P = 0.001), but not overall survival. There was a significant correlation between LRC and the EORTC (P = 0.02). The patients who achieved a complete response by the EORTC criteria showed significantly better PFS and overall survival (P = 0.01 and 0.04, respectively). The ΔLR was inferior to FDG PET-CT with respect to the prediction of patient survival; however, it may be useful for selecting patients in need of more aggressive monitoring after CRT.     

Ferrocene-containing cationic lipids for the delivery of DNA: oxidation state determines transfection activity.

The ability of two redox-active, ferrocene-containing cationic lipids [11-(ferrocenylundecyl)trimethylammonium bromide (FTMA) and bis(11-ferrocenylundecyl)dimethylammonium bromide (BFDMA)] to transfect mammalian cells was investigated. This study sought to determine the range of conditions over which these lipids were capable of transfecting cells and whether the oxidation state of the ferrocenyl groups in these materials could be used to influence the extent of transfection. Experiments conducted in the COS-7 cell line demonstrated that reduced and oxidized FTMA were substantially cytotoxic and did not transfect cells. Subsequent experiments conducted using BFDMA and reporter plasmids encoding enhanced green fluorescent protein (EGFP) and firefly luciferase demonstrated that BFDMA was able to transfect cells. However, the extent of transfection depended significantly upon both the concentration of BFDMA and the oxidation state of the lipid. Quantitative characterization of cytotoxicity and gene expression demonstrated that a window of concentration existed over which reduced BFDMA was non-cytotoxic and yielded high levels of transfection, but over which electrochemically oxidized BFDMA yielded very low (background) levels of transfection. Characterization of lipoplexes using dynamic light scattering demonstrated that reduced and oxidized BFDMA formed small aggregates (ca. 90 to 250nm) at concentrations of lipid ranging from 2 to 10 microM. Taken together, these results demonstrate that the oxidation state of BFDMA, which can be controlled electrochemically, can be used to control the extent of cell transfection. These results could form the basis of transfection procedures that exploit the redox behavior of ferrocene-containing lipids to achieve active spatial and temporal control over transfection using electrochemical methods.     

Monoclonal antibody analysis of glomerular, tubulo-interstitial infiltrating immune cells in various glomerulonephritis

To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis.     

Synthesis of antimicrobial agents. 3. Syntheses and antibacterial activities of 7-(4-hydroxypiperazin-1-yl)quinolones

A series of novel pyridone carboxylic acids having a 4-hydroxypiperazinyl group at the 7-position of norfloxacin and ciprofloxacin were prepared. The in vivo antibacterial efficacies of these compounds were superior to those of corresponding piperazinyl derivatives. From the results of the studies on the pharmacokinetic profile and toxicity, the 4-hydroxypiperazinyl derivatives were confirmed to be pharmacologically superior to corresponding piperazinyl derivatives. Thus, a 4-hydroxypiperazinyl group was revealed to be a beneficial substituent for potential use in future quinolone antibacterials.     

Diurnal patterns of serotonin, 5-hydroxyindoleacetic acid, tryptophan and fibrinolytic activity in blood of depressive patients and healthy volunteers.

Diurnal changes of serotonin-related factors in whole blood and fibrinolytic activity were determined in depressed patients and healthy controls. Whole blood serotonin concentration of depressed patients showed marked changes throughout daytime, with maximum values in the evening and lowest values in the morning, whereas its metabolite 5-HIAA followed a contrary pattern. The circadian rhythm of 5-HT and 5-HIAA in the control group was quite different from depressed patients. Plasma levels of tPA decreased from 12:30 to 16:30. Concentrations of free plasminogen activator inhibitor (PAI-1) and complex of tPA-PAI-1 decreased from 8:30 to 16:30. Plasma levels of total PAI-1 decreased from 8:30 to 16:30. Plasma levels of the fibrinolytic parameters may be lower in depressive patients than in normal controls. These results support the changes in the circadian rhythm of serotonin and its related substances in the blood of depressive patients.