An open trial of risperidone in autistic children

Clinical effects of risperidone were evaluated in 9 young autistic children under informed consent of their parents. The patients were evaluated by the Children's Behavioral Checklist and Rutter's Autistic Behavioral Rating Scale. After the administration, two subjects (playing and adaptation to change) of the Children's Behavioral Checklist and four (anomalous autistic behavior, destructive behavior, developmental problem and activity level) of the Rutter's Autistic Behavioral Rating Scale were improved significantly. There were no serious side effects such as extrapyramidal symptoms except minor adverse effects including sedation, depression, increased appetite and constipation. Risperidone might be effective for serious behavioral disturbances in young autistic children.     

Urokinase-type plasminogen activator is activated in stratum corneum after barrier disruption

The plasminogen/plasmin system in epidermis is thought to be the major protease involved in the delay of barrier recovery. However, little is known about the mechanism through which this system is activated. In order to clarify this mechanism, we first determined the distribution of proteolytic activity by using in situ zymography. As a result, plasminogen-activator activity was found to be present in the stratum corneum (SC) after barrier disruption. Next, SC subjected to repeated barrier disruption was collected to identify the protease. The protease was identified as urokinase-type plasminogen activator, because flybrinolytic activity of the collected SC was abolished by addition of anti-urokinase antibody. Urokinase activation in SC was confirmed by means of an in vitro assay, in which the precursor of urokinase (pro-uPA) became active after incubation with the insoluble component of SC homogenate. These findings indicated that urokinase-type plasminogen activator is activated in SC after barrier disruption and this activation might trigger the plasminogen/plasmin system in the epidermis.     

Enhanced expression of vascular endothelial growth factor by periodontal pathogens in gingival fibroblasts

Vascular endothelial growth factor (VEGF) has recently attracted attention as a potent inducer of vascular permeability and angiogenesis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. The aim of the present study was to investigate the properties of VEGF expression in human gingival fibroblasts (HGF) culture. HGF were stimulated with lipopolysaccharide (LPS), vesicle (Ve) and outer membrane protein (OMP) from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. HGF constitutively produced VEGF and levels were significantly enhanced (P < 0.01) by stimulation with Ve and OMP from A. actinomycetemcomitans and P. gingivalis at concentrations of 10 microg/ml or higher. On the other hand, VEGF levels were not increased by LPS stimulation. VEGF mRNA expression was also observed in Ve- and OMP-stimulated HGF. A vascular permeability enhancement (VPE) assay was performed using guinea pigs to ascertain whether supernatant from cultures of Ve- and OMP-stimulated HGF enhance vascular permeability in vivo. Supernatant from cultures of Ve- and OMP-stimulated HGF strongly induced VPE. This was markedly suppressed upon simultaneous injection of anti-VEGF polyclonal antibodies with the supernatant. Heating and protease treatment of the stimulants reduced the VEGF enhancing levels in Ve and OMP in vitro. These results suggest that Ve and OMP may be crucial heat-labile and protease-sensitive components of periodontal pathogens that enhance VEGF expression. In addition, VEGF might be associated with the etiology of periodontitis in its early stages according to neovascularization stimulated by periodontal pathogens causing swelling and edema.     

Effect of surface treatment and cement maturation on the bond strength of resin-modified glass ionomers to dentin

This study investigated the effect of surface treatment and cement maturation on the bond strength of resin-modified glass ionomer cements (RMGICs) to dentin. Forty-two freshly extracted premolars were embedded and horizontally sectioned at a level 2 mm from the central fossa to obtain a flat dentin surface. The premolars were randomly divided into three groups of 14 teeth and treated as follows: Group 1 (control)--no surface treatment, Group 2--conditioned with 20% polyacrylic acid for 10 seconds and Group 3--etched with 37% phosphoric acid for 15 seconds. RMGIC (Fuji II LC, GC) columns (3 mm diameter; 2 mm high) were applied to the dentin surface and shear bond testing was carried out after one week (n = 7) and one month (n = 7) storage in distilled water at 37 degrees C using an Instron Universal testing machine with a cross-head speed of 0.6 mm/minute. The failure mode was examined at 40x magnification and scored with imaging software. The results were analyzed using ANOVA/Scheffe's post-hoc test and Kruskal-Wallis/Mann-Whitney test at a significance level of 0.05. The effect of surface treatment on shear bond strength to dentin was time dependent. Mean strengths ranged from 3.16 to 5.81 MPa at one week and 5.00 to 14.95 MPa at one month. Although no significant difference in strengths was observed among the groups at one week, significant differences (Group 2 > Group 1 > Group 3) were detected at one month. At one month, conditioned and untreated specimens exhibited significantly less adhesive failure than etched specimens.     

Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis

Skeletal muscle is able to repair itself through regeneration. However, an injured muscle often does not fully recover its strength because complete muscle regeneration is hindered by the development of fibrosis. Biological approaches to improve muscle healing by enhancing muscle regeneration and reducing the formation of fibrosis are being investigated. Previously, we have determined that insulin-like growth factor-1 (IGF-1) can improve muscle regeneration in injured muscle. We also have investigated the use of an antifibrotic agent, decorin, to reduce muscle fibrosis following injury. The aim of this study was to combine these two therapeutic methods in an attempt to develop a new biological approach to promote efficient healing and recovery of strength after muscle injuries. Our findings indicate that further improvement in the healing of muscle lacerations is attained histologically by the combined administration of IGF-1 to enhance muscle regeneration and decorin to reduce the formation of fibrosis. This improvement was not associated with improved responses to physiological testing, at least at the time-points tested in this study.     

Uptake of indocyanine green by hepatocytes under inflow occlusion of the liver

BACKGROUND: It is not clear that hepatic venous backflow actually contributes to hepatic tissue oxygenation under inflow occlusion of the liver. In order to prove that substances delivered via the hepatic vein can be utilized and/or metabolized in hepatocytes during inflow occlusion, hepatic uptake in bile and excretion of indocyanine green (ICG) were investigated in pigs. MATERIALS AND METHODS: Animals were divided into two groups: an inflow occlusion (IO) group (N = 6) and a total hepatic vascular exclusion (THVE) group (N = 3) using a bypass. One milligram of ICG per kilogram body weight was administered at the beginning of blood flow occlusion, the retention rate in the blood (ICG R) measured, and the ICG in the hepatic tissue measured by near-infrared (NIR) spectroscopy. Furthermore, the ICG concentration was measured in bile excreted by intermittent perfusion of the liver. RESULTS: ICG R declined with time in both groups; however, ICG R in the IO group decreased much faster than in the THVE group. There were significant differences between the two groups after 30 min of occlusion (P < 0.05). ICG in the hepatic tissue could be detected as a peak at 805 nm 10 min after ICG injection, and the peak became steeper with time. On the other hand, ICG was not detected at all in the hepatic tissue after 180 min in the THVE group. ICG was excreted in the bile after 60 min under IO and increased with time. On the contrary, ICG was not excreted in the bile at all under THVE. There were significant differences between the two groups after 90 min (P < 0.05). CONCLUSION: These results indicate that ICG can be extracted in hepatocytes and excreted in bile under IO of the liver. Consequently, substances such as oxygen and drugs, which are delivered via the hepatic vein, can be utilized and/or metabolized in hepatocytes under IO.     

Changes in Mac-1 and CD14 expression on monocytes and serum soluble CD14 level during push/pull hemodiafiltration

BACKGROUND/AIM: Employment of treated dialysate as replacement fluid raises concerns about exposure of patients to pyrogenic substances. This study was undertaken to evaluate the safety of treated dialysate as the replacement fluid for push/pull hemodiafiltration. METHODS: In the present study, changes in the expressions of Mac-1 and CD14 on monocytes, which are upregulated by monocyte activation, were analyzed by flow cytometry, and the serum level of sCD14 which elevates by monocyte activation was measured by enzyme-linked immunosorbent assay (ELISA) during treatment in 7 patients on hemodialysis with regenerated cellulose (RC) membrane, polysulfone (PS) membranes and by push/pull hemodiafiltration (HDF) with PS membranes in a cross-over fashion. RESULTS: During hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration with PS, both Mac-1 and CD14 expressions on monocytes significantly increased by passing through the artificial kidneys, and, accordingly, the respective values downstream of the artificial kidneys were significantly higher than the predialysis values, even when the lipopolysaccharide level in dialysate was not detectable by Limulus assay. There was no significant variation in serum sCD14 levels during any of the hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration. However, during hemodialysis with PS or push/pull hemodiafiltration with PS, changes in Mac-1 and CD14 expression on monocytes were significantly smaller than those during hemodialysis with RC. CONCLUSION: Monocytes are activated to a greater extent during hemodialysis with RC membranes than during push/pull HDF with PS membranes. We consider that push/pull HDF may be safer than hemodialysis with RC membrane and that it is as safe as hemodialysis with the PS membrane in terms of monocyte activation, when pyrogen-free dialysate is employed.     

A comparison of the INVOS 4100 and the NIRO 300 near-infrared spectrophotometers

We determined whether two different devices for measuring near-infrared spectroscopy (NIRS)---the INVOS 4100 and the NIRO 300---produce similar cerebral oxygenation data during the CO(2) challenge test. Nineteen patients anesthetized with sevoflurane, 67% nitrous oxide in oxygen, and fentanyl were studied. A series of measurements of regional cerebral oxygen saturation (rSO(2)), measured by the INVOS 4100, and tissue oxygen index (TOI), measured by the NIRO 300, were performed in the following conditions: 1) normocapnia (PaCO(2), 35--45 mm Hg); 2) hypocapnia (PaCO(2), 25--35 mm Hg); 3) normocapnia; and 4) hypercapnia (PaCO(2), 45--55 mm Hg). Hemodynamic variables, including arterial blood gases and cerebral blood flow velocity, were measured at the same time with transcranial Doppler. The values and percentage changes of rSO(2) and TOI were compared by using regression analysis and Bland and Altman analysis. The rSO(2) showed a significant positive correlation with TOI (r = 0.58, P < 0.01). The percentage change of rSO(2) also showed a significant positive correlation with the percentage change of TOI during the CO(2) challenge (r = 0.85, P < 0.01). Bland and Altman analysis revealed a bias of -0.5% with 2 SD of 15.6% when comparing the rSO(2) value with the TOI value, and it showed a bias of -3.4% with 2 SD of 15.2% when comparing the percentage change of rSO(2) with the percentage change of TOI, indicating unacceptable disagreement of these data. These results indicate that cerebral oxygen saturation and its relative change during the CO(2) challenge may vary depending on the type of NIRS used. Because the measurement technique and algorithm were different in each device, we should carefully consider the clinical application of the values produced by NIRS. IMPLICATIONS: Near-infrared spectroscopy (NIRS) has been proposed as a noninvasive clinical method for assessing cerebral oxygenation. The acceptable reliability and validity of NIRS values have not been established despite their widespread use. The INVOS 4100 and the NIRO 300 can display cerebral oxygen saturation as regional cerebral oxygen saturation and tissue oxygenation index, but they produce differing results.