Mathematical modeling of calcium waves induced by mechanical stimulation in keratinocytes.

Recent studies have shown that the behavior of calcium in the epidermis is closely related to the conditions of the skin, especially the differentiation of the epidermal keratinocytes and the permeability barrier function, and therefore a correct understanding of the calcium dynamics is important in explaining epidermal homeostasis. Here we report on experimental observations of in vitro calcium waves in keratinocytes induced by mechanical stimulation, and present a mathematical model that can describe the experimentally observed wave behavior that includes finite-range wave propagation and a ring-shaped pattern. A mechanism of the ring formation hypothesized by our model may be related to similar calcium propagation patterns observed during the wound healing process in the epidermis. We discuss a possible extension of our model that may serve as a tool for investigating the mechanisms of various skin diseases.

The effect of losartan and amlodipine on left ventricular diastolic function and atherosclerosis in Japanese patients with mild-to-moderate hypertension (J-ELAN) study.

This study was a prospective, randomized, open, blinded endpoint study to assess the effects of angiotensin II type 1 receptor blocker, losartan, compared with calcium channel blocker, amlodipine, on left ventricular (LV) diastolic function and atherosclerosis of the carotid artery in Japanese patients with mild-to-moderate hypertension, LV hypertrophy, diastolic dysfunction and preserved systolic function. Fifty-seven patients were randomly assigned to losartan- or amlodipine-based treatment groups and were followed up for 18 months. Blood pressure was similarly reduced by both regimens. Losartan shortened the transmitral E-wave deceleration time, and amlodipine reduced LV mass index; however, there was no significant difference in the percent changes of these indices between the two groups. Mean carotid intima-media thickness (mean IMT) as well as plaque score significantly increased in the amlodipine-based regimen (pre: 1.05±0.26 mm, follow-up: 1.23±0.33 mm, P=0.0015), but not in the losartan-based regimen (pre: 1.08±0.35 mm, follow-up: 1.16±0.52 mm, P=non-significant). The percent increase in mean IMT in the amlodipine-based regimen tended to be large compared with the losartan-based regimen (amlodipine: 19.8±23.7%, losartan: 6.9±23.3%, P=0.06). Under similar reduction of blood pressure, losartan is likely effective in protecting the progression of atherosclerosis of the carotid artery compared with amlodipine. Losartan may improve LV diastolic function, and amlodipine may attenuate LV hypertrophy; however, this study cannot make consecutive remarks about the superiority of either treatment regimen in the effects on cardiac function and geometry. This study has been registered at http://www.umin.ac.jp/ctr/listj/ (identifier C000000319).

[High incidence of cardiorespiratory deterioration in patients receiving cemented hip hemiarthroplasty for femoral neck fracture].

BACKGROUND: Anesthesia for patients who undergo surgery for femoral neck fractures can be associated with severe cardiopulmonary complications. METHODS: We retrospectively studied 361 consecutive patients who underwent surgery for femoral neck fractures. Dividing patients into three groups according to type of surgery-hip hemiarthroplasty (n=134), compression hip screw (n=123) or gamma nail (n=104)--we calculated the incidences of cardiorespiratory deterioration during anesthesia and examined factors associated with it. RESULTS: Among hemiarthroplasty patients, six (4.5%) encountered cardiorespiratory deterioration; four (3.0%) experienced profound hypotension, bradycardia or cardiac arrest immediately after implantation of the bone cement or insertion of the prosthesis into the femoral bone; and two (1.5%) developed hypoxia and angina pectoris during the late phase of surgery. Patients who underwent compression hip screw or gamma nail had no cardiorespiratory deterioration. No difference was found in patient characteristics or type of anesthesia used among the three surgery groups. Time of surgery and amount of blood loss both were significantly greater in patients undergoing hemiarthroplasty. CONCLUSIONS: The surgical techniques selected for hip hemiarthroplasty, which is associate with an increase in intramedullary pressure, may be a significant risk factor for cardiorespiratory deterioration from anesthesia in patients undergoing surgery for femoral neck fracture.

Profiling the cytokines in gingival crevicular fluid using a cytokine antibody array.

BACKGROUND: Various compounds have been detected in gingival crevicular fluid (GCF) as indicators of periodontal disease activity. Therefore, the analysis of GCF may be especially beneficial for diagnosing current periodontal status and addressing the effects of treatment. Moreover, the identification of new markers in GCF may also contribute to elucidating novel mechanisms involved in periodontal disease. This study sought novel marker proteins specific to chronic periodontitis by profiling cytokines in GCF using a cytokine antibody array system. METHODS: Human cytokine array V, which detects 79 cytokines on one membrane, was used to determine the profile of cytokines in GCF from seven subjects with chronic periodontitis and seven subjects with healthy periodontia. The profile was exposed to x-ray film and quantified using image analysis software. Healthy and diseased sites were compared statistically. RESULTS: We detected 10 cytokines in periodontally healthy sites and 36 cytokines in periodontally diseased sites. Interleukin-8 (IL-8) and transforming growth factor-beta 2 (TGF-beta2) were detected at high levels in healthy and diseased subjects. There were significant differences between healthy and diseased subjects in the levels of tissue inhibitor of metalloproteinases-2 (TIMP-2), tumor necrosis factor-beta (TNF-beta), growth-related oncogene (GRO), interferon-inducible protein-10 (IP-10), angiogenin (Ang), vascular endothelial growth factor (VEGF), insulin-like growth factor binding protein-3 (IGFBP-3), osteoprotegerin (OPG), epidermal growth factor (EGF), glial-derived neurotrophic factor (GDNF), pulmonary and activation-regulated chemokine (PARC), oncostatin M (OSM), fibroblast growth factor-4 (FGF-4), IL-16, homologous to lymphotoxins (LIGHT), and placenta growth factor (PlGF). Of these, the newly detected cytokines were GRO, Ang, IGFBP-3, GDNF, PARC, OSM, FGF-4, IL-16, LIGHT, and PlGF. CONCLUSIONS: In this study, we detected several cytokines in GCF using a cytokine antibody array system, including both inflammatory cytokines and various growth factors. Therefore, periodontal disease may participate in the wound healing process and in tissue destruction via the inflammatory process. Our results suggest that the quantification of these cytokines in GCF provides useful information for the diagnosis of periodontal disease status.

[Use of propofol for carotid endarterectomy: its effect on parameters of intraoperative monitoring and clinical outcomes].

In order to evaluate the effects of propofol on neurologic outcomes of patients for carotid endarterectomy (CEA), intraoperative monitoring and postoperative complications were evaluated. Fifty two CEA cases were divided into two groups according to the method of anesthesia; group P (+) using propofol (n = 26), and group P (-) without propofol (n = 26). During cross-clamping of the internal carotid artery, oxygen saturation of internal jugular vein (SjO2) and somatosensory evoked potentials(SEP) were monitored continuously on the operated side. Moreover, the patients with postoperative neurological complications were examined for each parameter. There were no significant differences between the two groups in %SjO2, %SEP and number of cases with neurologic deficits. In the patients with poor outcomes, the value of stump pressure (SP) was significantly lower. We conclude that propofol had no significant effect against neurological complications in CEA patients, and SP monitoring was effective for evaluation of the clinical outcome in CEA patients.

Comparison of time of reperfusion during anterior wall acute myocardial infarction to left ventricular volume one month and 20 months later.

We studied 95 patients with a first anterior wall acute myocardial infarction who received successful reperfusion within 72 hours after the onset. The patients were divided into 4 groups based on the time required to achieve reperfusion; <3 hours (n = 23), 3 to 6 hours (n = 42), 6 to 24 hours (n = 17), and >24 to 72 hours (n = 13). The infarct size, as evaluated by thallium-201 single-photon emission computed tomography, at 1 month after the infarct was significantly larger (p <0.05) in >24 to 72 hours (1,593 +/- 652 U) than that in <3 hours (749 +/- 650 U), but was not significantly different from that at 3 to 6 hours (1,353 +/- 770 U) or 6 to 24 hours (1,371 +/- 561 U). The end-diastolic volume index at 1 month did not differ among the 4 groups. However, the end-diastolic volume index during the follow-up period (20 +/- 8 months) in >24 to 72 hours (93 +/- 23 ml/m(2)) was significantly larger than that in the other 3 groups (<3 hours [65 +/- 21 ml/m(2)], 3 to 6 hours [65 +/- 22 ml/m(2)], and 6 to 24 hours [70 +/- 25 ml/m(2)]). Similar findings were observed in end-systolic volume index. In conclusion, although infarct size reduction was not observed by late reperfusion, left ventricular volumes at 1 month were comparable among patients with successful reperfusion within 3 and up to >24 hours. Left ventricular volumes 2 years after acute myocardial infarction were significantly larger in patients who did not under reperfusion for >24 hours.

[Changes of blood volume and blood propofol concentration during the anesthetic management of a pheochromocytoma patient].

A 44-year-old man with right pheochromocytoma was scheduled for tumor resection. General anesthesia was maintained with nitrous oxide (66%), oxygen (33%), continuous infusion of propofol (4 mg.kg-1.hr-1), and continuous epidural block (1.5% mepivacaine 4 ml.hr-1). During operation, cardiac output and blood volume (BV) were measured by pulse dye-densitometry using DDG-2001 (Nihon Kohden, Japan), and arterial and mixed venous blood concentrations of propofol were measured by high performance liquid chromatography (HPLC). After tumor resection, cardiac output increased without change in BV, on the other hand, both arterial and mixed venous blood propofol concentrations clearly decreased. In conclusion, during the anesthetic management with propofol in case of pheochromocytoma, attention should be paid to depth of anesthesia because of changing propofol blood concentration.

Hepatocyte growth factor (HGF) in periodontal disease: detection of HGF in gingival crevicular fluid.

Hepatocyte growth factor (HGF) acts as a mitogen, motogen, morphogen, anti-apoptotic factor, and scatter factor for various kinds of epithelial cells. It is a protein secreted by mesenchymal cells such as fibroblasts, and promotes motility and matrix invasion of epithelial cells. To clarify whether HGF is involved in periodontal disease, this study was conducted to determine whether HGF is present in gingival crevicular fluid (GCF) and to investigate the relationship between levels of HGF and the clinical parameters of periodontal disease, probing depth (PD), gingival index (GI) and bleeding on probing (BOP). We examined and collected GCF samples from 80 sites in 38 subjects with periodontal or other oral diseases. The concentrations of HGF, IL-1beta and PGE2 were determined by ELISA, and active collagenase activity was determined by functional assay. The HGF level correlated positively with PD and GI, and was significantly higher in specimens from BOP-positive sites and those where PD exceeded 4 mm compared with those from sites that were BOP-negative or with a PD less than 3 mm. There was a significant positive correlation between the concentrations of HGF and IL-1beta. These results indicate that the HGF level in GCF correlates well with clinical parameters of periodontal disease, and suggest that HGF may be involved in epithelial invasion through its role as a scatter factor.

Hepatocyte growth factor (HGF) system in gingiva: HGF activator expression by gingival epithelial cells.

Hepatocyte growth factor (HGF) acts as a mitogen, motogen, morphogen, and anti-apoptotic factor for various kinds of epithelial cells. We previously showed that periodontal ligament and gingival fibroblasts secreted an HGF-like chemoattractant for a gingival epithelial cell line and found that the HGF content of gingival crevicular fluid was well correlated with clinical parameters and interleukin-1beta level. Since HGF is secreted as an inactive form (proHGF), and converted to an active form by serine proteases such as HGF activator (HGFA), extracellular processing of proHGF is presumed to be critical in the regulation of HGF activity. To examine the role of the HGF system in epithelial invasion followed by loss of connective tissue attachment in periodontitis, mRNA expression of HGF, its receptor (c-met) and HGFA in gingival tissues was monitored. Ten gingival biopsies were obtained, and epithelium and connective tissues were separated by enzymatic digestion. The gene expression of HGF and keratinocyte growth factor (KGF) in gingival connective tissue, and c-met, HGFA and KGF receptor (KGFR) in gingival epithelial tissues was monitored using RT-PCR. Furthermore, HGFA protein in the conditioned medium of cultured primary gingival epithelial cells was examined using Western blotting. All the connective tissue samples expressed KGF, and 8 out of 10 samples expressed HGF. All the epithelial samples expressed KGFR and c-met, whereas 5 out of 10 samples expressed HGFA. Protein expression of HGFA by cultured primary gingival epithelial cells was also confirmed. In terms of local production and activation of HGF in gingival tissue, these results suggest that synergistic expression of HGF in connective tissue and HGFA expression in epithelium may contribute to disease progression in periodontitis.