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Objective: To investigate the effect of a novel topical wound-healing agent, low-concentration povidone-iodine ointment (LPIO) with a hydrophobic white petrolatum-rich base on skin-wound models in rats and rabbits. Method: The therapeutic efficacy of topically applied LPIO was compared to that of standard-concentration povidone-iodine ointment (SPIO) and non-treatment control, using a full-thickness skin-wound model in 24 hairless rats and a full-thickness skin-defect model in rabbit earlobes. The animals were kept under standardised conditions at the Central Research Laboratory of Maruishi Pharmaceutical Co. Ltd. (Osaka, Japan). Therapeutic efficacy was evaluated based on macroscopic wound-size reduction, as well as histopathological and immuno-histochemical examinations. Results: LPIO enhanced wound healing in rat full-thickness skin ulcers, reducing wound size and inflammation, when compared with that in SPIO and non-treatment control. LPIO also markedly improved wound healing in rabbit earlobe ulcers by significantly improving re-epithelialisation, compared with that in SPIO. Conclusion: The results of this study suggest that LPIO is a useful topical therapy for ulcerative lesions. [ABSTRACT FROM AUTHOR]

Background 1,24-Dihydroxyvitamin D3 (tacalcitol), a vitamin D3 compound, has been used to treat T cell-mediated inflammatory skin diseases such as psoriasis, prurigo and vitiligo. The best-known mechanism of action of this compound is inhibition of the abnormal proliferation of keratinocytes and subsequent maturation; however, its effects on skin T-cell recruitment have not yet been evaluated. Cutaneous lymphocyte-associated antigen (CLA), a surface glycoprotein expressed on T cells, plays a critical role in skin T-cell infiltration. We recently reported that 1,25-dihydroxyvitamin D3 inhibits skin infiltration of CD4+ T cells by suppressing CLA expression on T cells. Objectives In this study, we investigated the effect of tacalcitol on CLA epitope decoration and on the levels of gut or lymph node homing receptor expression in human T cells. Methods We cultured human T cells with tacalcitol and analysed the effect on CLA expression and skin-homing ability, and evaluated glycosyltransferase mRNAs. We also performed an in vivo study using an antigen-dependent delayed-type hypersensitivity (DTH) mouse model and investigated the effect of tacalcitol on skin-infiltrating CD4+ T cells. Results Tacalcitol downregulated the expression of CLA and, in parallel, the E- and P-selectin ligand function; however, it exerted no effect on other homing receptors. Subcutaneously and intraperitoneally administered tacalcitol downregulated skin infiltration of effector CD4+ T cells in an in vivo DTH mouse model. Conclusions These findings suggest that tacalcitol reduces skin inflammation by partially downregulating CLA expression levels. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is a chronic disease with a Th2-type-cytokine dominant profile. Several cytokines and related peptides have been used for the treatment of AD but they were ineffective because of their limited biological half-life. We have recently developed a highly efficient mouse dominant negative interleukin (IL)-4/IL-13 antagonist (IL-4DM), which blocks both IL-4 and IL-13 signal transductions. Objective To examine the effects of IL-4DM in vivo in an AD model induced by the repeated exhibition of oxazolone (OX). Methods Plasmid DNA was injected intraperitoneally to cause an experimental AD-like dermatitis. The effect was evaluated by ear thickness, histological findings, and mast cells counts in the inflamed skin. The plasma IgE and histamine levels were measured. Cytokine production in skin and splenocytes were also analysed. Results Mice treated with control plasmid developed marked dermatitis with mast cells and eosinophil infiltration, and had increased plasma IgE and histamine levels with a Th2 type splenocyte cytokine profile. Treatment with mouse IL-4 DNA augmented the ear swelling and thickness with an increased dermal eosinophil count, plasma histamine level, and production of splenocyte IL-4. However, IL-4DM treatment successfully controlled the dermatitis, decreased the mast cell and eosinophil count, and suppressed plasma IgE and histamine levels. Splenocytes produced an increased level of IFN-γ. Conclusion These data showed that the simultaneous suppression of IL-4/IL-13 signals successfully controlled Th2-type chronic dermatitis. IL-4DM DNA treatment is a potent therapy for AD and related diseases. [ABSTRACT FROM AUTHOR]

Background: We recently reported that human protein C inhibitor (PCI), a major inhibitor of activated protein C (APC), inhibits hepatocyte growth factor activator (HGFA) by forming HGFA--PCI complexes in vitro. In this study, we evaluated whether PCI regulates HGFA-mediated liver regeneration in a human PCI gene transgenic (hPCI-Tg) mouse model. Methods and results: After partial hepatectomy in hPCI-Tg and wild-type (WT) mice, the degree of liver regeneration, protein and mRNA expression of HGFA, proHGF activation, plasma levels of PCI and HGFA--PCI complex, and other markers were evaluated in the remnant liver. We also evaluated the effect of anti-human PCI antibody on liver regeneration, which significantly decreased in hPCI-Tg mice compared to WT mice. HGFA mRNA levels in naive and remnant livers after hepatectomy were the same in both WT and hPCI-Tg mice; however, plasma HGFA levels and HGF activation in the liver were lower in hPCI-Tg than in WT mice. There was no difference in plasma levels of transaminases and inflammatory cytokines. However, sinusoidal congestion and bleeding were detected and the serum hyaluronic acid level was elevated in hPCI-Tg mice, indicating that human PCI aggravates sinusoidal injury by inhibiting the cytoprotective effect of APC. APC decreased thrombin-induced IL-6 production in isolated hepatic nonparenchymal cells (NPCs) in vitro. This impaired liver regeneration was reversed by anti-human PCI antibody treatment in vivo. Conclusion: PCI regulates liver regeneration after hepatectomy by forming an HGFA--PCI complex and aggravates hepatic NPC injury by inhibiting the cytoprotective effect of APC. Anti-PCI antibody treatment may be a novel therapy for improving liver regeneration. [ABSTRACT FROM AUTHOR]

Aims Activated protein C (APC) is a key regulator of the clotting system and immune responses. We studied the relationship between the degree of atherosclerosis as measured by the intima-media thickness (IMT) of carotid artery and APC generation in Type 2 diabetic patients. Methods Eighty-seven Type 2 diabetic patients and 35 control subjects participated. APC generation was assessed by the plasma APC–protein C inhibitor complex (APC-PCI) levels and the mean IMT of carotid artery was measured by ultrasonography. The plasma levels of the thrombin–anti-thromobin complex (TAT) and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunoassays. Results Plasma TAT levels were significantly higher in diabetic patients [2.03 (1.12, 2.56) ng/ml, median (25th, 75th percentile)] compared with control subjects [0.85 (0.55, 2.08) ng/ml, P < 0.01]. Plasma APC-PCI levels were significantly lower in diabetic patients [0.93 (0.74, 1.22) ng/ml], than in control subjects [1.66 (1.25, 2.36) ng/ml, P < 0.001]. The mean IMT was significantly increased in diabetic patients (0.881 ± 0.242 mm; mean ± sd) compared with control subjects (0.669 ± 0.140 mm; P < 0.01). Univariate analysis showed a significant and inverse correlation between plasma APC-PCI levels and mean IMT ( r = –0.32, P < 0.005), and multivariate regression analysis confirmed the independent correlation ( P < 0.05). Moreover, plasma APC-PCI levels significantly and inversely correlated with plasma PDGF levels in diabetic patients ( r = –0.30, P < 0.01). Conclusions These results suggest that decreased APC generation is associated with vascular atherosclerotic changes in Type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Several studies have shown that reflux esophagitis (RE) occurs after eradication of Helicobacter pylori . However, endoscopic findings do not allow prediction of the development of RE after successful treatment. In this study, we evaluated the relationship between the prevalence of RE after eradication therapy and the degree of hiatal hernia. Methods: The study comprised 148 patients who had undergone H. pylori eradication therapy over the past 5 years. The degree of RE and hiatal hernia was evaluated based on endoscopic findings. Hiatal hernia was graded according to Hill's gastroesophageal flap valve (GEFV; grades I-IV) classification. RE after eradication therapy was graded according to the Los Angeles classification system. H. pylori infection was confirmed in all patients by culture, urease test and histological examination of antral and fundic biopsy specimens. Results: Among 148 patients, there were 122 patients (82.4%) with successful and 26 (17.6%) with failed eradication therapy. RE was diagnosed in 25 (20.5%) out of 122 patients with successful therapy but only in 1 (3.8%) out of 26 patients with failed therapy ( P < 0.05). After successful eradication, 25 patients had mild RE (12 with grade A, 13 with grade B). Among patients of the successful eradication group ( n = 122), RE was diagnosed in 2 (5.3%) out of 38 patients without hiatal hernia and in 23 (27.4%) out of 84 patients with hiatal hernia ( P = 0.0051). Furthermore, RE was diagnosed in 2 (5.3%) out of 38 patients with GEFV grade I, 13 (24.1%) out of 54 with grade II, 7 (30.4%) among 23 with grade III, and 3 (42.9%) out of 7 patients with grade IV. The pH level of gastric juice after eradication therapy was lower in the group with successful eradication than in the group with failed therapy regardless of the incidence and degree of RE. Conclusions: There is a high incidence of RE after successful H. pylori eradication therapy. This incidence of RE was closely associated with the presence and degree of hiatal hernia and with the decrease in gastric juice pH. These findings suggest that the presence of hiatal hernia together with increase in gastric acidity are important determinant factors for the development of RE after successful H. pylori eradication therapy. [ABSTRACT FROM AUTHOR]

Studies the potential usefulness of methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) as an anti-cancer agent in gastric cancer. Effect of MGBCP treatment in the growth of cancer cell lines; List of intracellular mediators for proliferation of cancer cells; Details on the role of intracellular polyamine levels in triggering apoptosis.

Objective: To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes.Research Design and Methods: The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (approximately 1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization.Results: Univariate regression analysis disclosed a significant correlation between log-transformed HOMA-IR and log-transformed clamp IR before (r = -0.613, P < 0.0001) and after ( = -0.734, P < 0.0001) treatment. Neither the slopes (-0.71 +/- 0.12 vs. -0.79 +/- 0.09, F = 0.25, P = 0.61) nor the intercepts (y-intercept = 1.67 vs. 1.70, x-intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log-transformed HOMA-IR and the increase in clamp IR during treatment (r = -0.617, P < 0.0001).Conclusions: HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

SummaryAim To determine the relationship of the polymorphism at codon 54 of the intestinal fatty acid binding protein gene (FABP2) with insulin resistance and susceptibility to Type 2 diabetes mellitus (DM) in the Japanese population. Methods We evaluated the polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 150 Type 2 DM patients and 147 healthy control subjects. The frequency of alleles encoding threonine (Thr54) and alanine (Ala54) at codon 54 of FABP2 in Type 2 DM patients was compared with that of healthy controls. Insulin sensitivity was assessed by the hyperinsulinaemic euglycaemic clamp in Type 2 DM patients with Ala54 homozygotes, Ala54/Thr54 heterozygotes and Thr54 homozygotes and by homeostasis model assessment (HOMA) in the nondiabetic group. Results The frequency of alleles encoding Ala54 and Thr54 was 0.59 and 0.41 in Type 2 DM patients, respectively, similar to that observed in nondiabetic controls (0.64 for Ala54 and 0.36 for Thr54). Insulin sensitivity was not significantly different between subjects with and without Thr54 allele either within the DM group or healthy controls. Conclusions The allele encoding threonine in the FABP2 does not predispose to Type 2 DM or insulin resistance in the Japanese population Diabet. Med. 16, 119–124 (1999). [ABSTRACT FROM AUTHOR]

Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen ( p < 0.02), prothrombin fragment 1 + 2 ( p < 0.05), fibrin monomer ( p < 0.0001), protein C antigen ( p < 0.005), total protein S antigen ( p < 0.02), soluble thrombomodulin ( p < 0.005) and soluble E-selectin ( p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 ± 3.8 vs 3.0 ± 0.4 pmol/l) was significantly higher ( p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 ± 2.6 vs 35.3 ± 3.0 ng/ml) was markedly lower ( p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 ± 0.6 vs 8.6 ± 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 ± 2.9 vs 23.4 ± 2.6 %, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin. [Diabetologia (1996) 39: 1455-1461] [ABSTRACT FROM AUTHOR]

Focuses on a study on the associations of levels of atrial natriuteric peptide and brain natriuteric peptide with renin activity in diabetic patients. Mechanisms which may affect renin release; Results; Indication of the study results.

SummaryWe evaluated the effect of troglitazone (given orally 400 mg/day) on glucose intolerance and on the plasma levels of tumour necrosis factor-α (TNF-α) in 12 obese patients with type 2 diabetes for 12 weeks. Troglitazone significantly decreased fasting plasma glucose, serum C-peptide, serum insulin and HbA1c levels. Plasma levels of TNF-α were significantly reduced by troglitazone administered for 8 and 12 weeks. Troglitazone administration significantly improved insulin resistance, but did not affect pancreatic β-cell function as evaluated by the homeostasis model assessment (HOMA). In the present study, we reported for the first time that troglitazone administration significantly reduces plasma levels of TNF-α in obese patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: The peripheral blood concentrations of several proteases of the clotting system have been shown to predict survival in patients with malignancy. A study was undertaken to investigate the independent value of the plasma levels of the D-dimer degradation product of fibrin before treatment for predicting prognosis in patients with lung cancer.Methods: The study comprised 70 patients with lung cancer (49 non-small cell lung cancer and 21 small cell lung cancer). Plasma levels of D-dimer were measured using an enzyme immunoassay kit. Multivariate statistical analysis was carried out using the Cox's proportional hazards model.Results: The median value of the plasma level of D-dimer differentiated two groups of patients with different outcomes: a group with a D-dimer level of < 150 ng/ml (low DD group) and those with D-dimer levels of > or = 150 ng/ml (high DD group). Survival time was significantly better in patients in the low DD group than in those in the high DD group in all patients (hazard ratio for high DD group = 4.7; 95% confidence interval (CI) 1.8 to 11.7). The plasma levels of D-dimer predicted survival independently from the clinical stage of disease, histological type, performance status, and tumour size (hazard ratio = 3.9; 95% CI 1.6 to 9.2).Conclusions: These results suggest that plasma levels of D-dimer might be useful for predicting the clinical outcome in patients with lung cancer. However, further prospective studies are needed in a larger population to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the usefulness of CT for assessing oxygen desaturation during walking in patients with emphysema.Material and Methods: The study comprised 32 patients with emphysema (mean age 67+/-6 years). Serial CT images of 5 mm were obtained from the apex to the basal regions of the lung during deep inspiration. The severity of emphysema was scored by four physicians according to a visual method. A six-minute walking test and oxygen desaturation (pSO2) measurements were performed.Results and Conclusion: The mean CT score of the four observers was significantly correlated with the nadir pSO2 and deltapSO2, but did not correlate with the total distance walked. These results suggest that CT may be used for the assessment of oxygen desaturation during low-grade exercise in patients with emphysema. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, e41-e46 (2012) Abstract Aims Dehydroepiandrosterone exerts a protective effect against cardiovascular diseases. However, the relationship of dehydroepiandrosterone with the anticoagulant factor activated protein C, generated by the thrombin-thrombomodulin complex on vascular endothelial cells, remains unknown. This study aimed at studying the relationship between dehydroepiandrosterone and activated protein C generation in patients with Type 2 diabetes. Methods Sixty-two male patients with Type 2 diabetes were enrolled in this study. Data obtained from 40 healthy male subjects were used as controls. The plasma levels of dehydroepiandrosterone, the activated protein C-protein C inhibitor complex, high-sensitivity C-reactive protein and monocyte chemoattractant protein-1 were measured by enzyme immunoassays. Carotid intima-media thickness was measured by ultrasonography. Results The plasma levels of dehydroepiandrosterone (5.15 ± 2.81 vs. 3.76 ± 2.16 ng/ml; P < 0.005) and the activated protein C-protein C inhibitor complex (1.90 ± 1.07 vs. 1.02 ± 0.51 ng/ml; P < 0.001) were significantly lower in patients with diabetes than in normal subjects. Univariate analysis showed a significant correlation of the plasma level of dehydroepiandrosterone with that of the activated protein C-protein C inhibitor complex ( r = 0.48, P < 0.001), high-sensitivity C-reactive protein ( r = −0.30, P < 0.05) and with the mean intima-media thickness ( r = −0.28, P < 0.05) in patients with diabetes. Stepwise multiple regression analysis showed that the plasma level of dehydroepiandrosterone is significantly correlated with the plasma levels of the activated protein C-protein C inhibitor complex ( F = 18.06) and high-sensitivity C-reactive protein ( F = 4.94). There was no correlation between the plasma levels of dehydroepiandrosterone and monocyte chemoattractant protein-1. Conclusions These results suggest that lower circulating levels of dehydroepiandrosterone are associated with decreased activated protein C generation and higher intima-media thickness in patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]