The effect of hesperidin supplementation on inflammatory markers in human adults: A systematic review and meta-analysis of randomized controlled clinical trials.

BACKGROUND: Hesperidin (a flavanone found in citrus fruits) supplementation is suggested to inversely affect inflammation; however, clinical trials have led to inconsistent results. OBJECTIVE: To examine the effect of hesperidin supplementation on inflammatory markers using systematic review and meta-analysis of randomized controlled clinical trials (RCTs). PATIENT AND METHODS: Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched up to December 2018. A random-effects model was used to compare the mean changes in the inflammatory markers between hesperidin supplemented and control subjects. RESULTS: Six eligible RCTs with 296 participants were included in the systematic review. The meta-analysis revealed that hesperidin significantly reduces Vascular Cell Adhesion Molecule 1 (VCAM-1) levels [weighted mean difference (WMD) = -22.81 ng/L, P = 0.041, n = 3]. No considerable changes was observed for serum C-reactive protein (CRP) levels (WMD = -0.69 mg/L, P = 0.079, n = 5); the subgroup analysis showed a significant reduction in studies with a parallel design (WMD = -0.72 mg/L, P = 0.024, n = 3), and studies with more than 4 weeks of follow-up (WMD = -0.76 mg/L, P = 0.020, n = 2). Hesperidin supplementation had no signification effect on circulating E-selectin, interleukin 6, and Intercellular Adhesion Molecule 1 (ICAM-1) levels. CONCLUSION: The present study suggests that although hesperidin supplementation significantly improves VCAM-1 levels; however, other inflammatory markers might not be affected. Further high-quality systematic reviews exploring the effect of hesperidin particularly on VCAM-1, ICAM-1, E-selectin, and interleukin 6 are still needed to confirm these results.

Lavender Essential Oil and Its Main Constituents Inhibit the Expression of TNF-α-induced Cell Adhesion Molecules in Endothelial Cells.

Lavender essential oil (Lvn) has anti-inflammatory effects in an ovalbumin-sensitized murine model of asthma, and inhibits inflammatory cell infiltration into the lungs. The anti-inflammatory effects of Lvn on cell adhesion molecules are not clear. Here we evaluated the effects of Lvn and its main constituents, linalyl acetate (LA) and linalool (LO), on the expression of tumor necrosis factor-alpha (TNF-α)-induced cell adhesion molecules in murine brain endothelial bEnd.3 cells and human umbilical vein endothelial cells (HUVECs). The bEnd.3 cells were treated with Lvn, LA, or LO and subsequently stimulated with TNF-α. The mRNA expression levels of cell adhesion molecules were detected using RT-PCR. E-selectin and P-selectin protein and phosphorylated-NF-κB p65 were detected by western blotting. The effects of Lvn on HUVECs were measured by RT-PCR. In bEnd.3 cells, Lvn and LA suppressed TNF-α-induced E-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and phosphorylated-NF-κB p65 in the nucleus; LO did not suppress P-selectin or phosphorylated-NF-κB p65. Lvn inhibited TNF-α-induced E-selectin mRNA in HUVECs. These results indicate that Lvn and LA inhibit TNF-α-induced cell adhesion molecules in endothelial cells through the suppression of NF-κB activation. Consequently, Lvn or other essential oils including LA may be useful as alternative anti-inflammatory medicines.

PPARα (Peroxisome Proliferator-activated Receptor α) Activation Reduces Hepatic CEACAM1 Protein Expression to Regulate Fatty Acid Oxidation during Fasting-refeeding Transition.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed at high levels in the hepatocyte, consistent with its role in promoting insulin clearance in liver. CEACAM1 also mediates a negative acute effect of insulin on fatty acid synthase activity. Western blot analysis reveals lower hepatic CEACAM1 expression during fasting. Treating of rat hepatoma FAO cells with Wy14,643, an agonist of peroxisome proliferator-activated receptor α (PPARα), rapidly reduces Ceacam1 mRNA and CEACAM1 protein levels within 1 and 2 h, respectively. Luciferase reporter assay shows a decrease in the promoter activity of both rat and mouse genes by Pparα activation, and 5'-deletion and block substitution analyses reveal that the Pparα response element between nucleotides -557 and -543 is required for regulation of the mouse promoter activity. Chromatin immunoprecipitation analysis demonstrates binding of liganded Pparα toCeacam1promoter in liver lysates ofPparα(+/+), but notPparα(-/-)mice fed a Wy14,643-supplemented chow diet. Consequently, Wy14,643 feeding reduces hepatic Ceacam1 mRNA and CEACAM1 protein levels, thus decreasing insulin clearance to compensate for compromised insulin secretion and maintain glucose homeostasis and insulin sensitivity in wild-type mice. Together, the data show that the low hepatic CEACAM1 expression at fasting is mediated by Pparα-dependent mechanisms. Changes in CEACAM1 expression contribute to the coordination of fatty acid oxidation and insulin action in the fasting-refeeding transition.

[Screening for differentially-expressed proteins in ovary of primary dysmenorrheal mice with Xiangfu Siwu decoction administration using nano LC-LTQ-Orbitrap-MS/MS].

To study the mechanism of Xiangfu Siwu decoction in treating primary dysmenorrhea, differentially-expressed proteins in ovary of primary dysmenorrheal mice with Xiangfu Siwu decoction administration were screened based on proteome technology using nano LC-LTQ-Orbitrap-MS/MS. Estradiol benzoate and oxytocin were used to produce dysmenorrheal mice model. The model mice were orally administrated with Xiangfu Siwu decoction for 3 days, and 1 h after the last administration, the ovary samples were collected. After protein denaturation, reduction, alkylation, desalination and enzymatic hydrolysis, identification was carried out by nano LC-LTQ-Orbitrap-MS/MS technology. The obtained data was processed by using Thermo Proteome discoverer 1.4 software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed. The significant differentially-expressed protein was checked using Western blot technology in ovary samples. A total of 106 differentially-expressed proteins were identified during the normal, model and administration group. Most of them participate cellular processes. Adherens junction and focal adhesion pathways play a regulatory role in various cell signaling pathways. Protein ADRM1 was validated. Compared to the normal group, it was up-regulated expression in the model group. After administration, the expression of ADRM1 was down-regulated. Through the comparative analysis, a series of differentially-expressed proteins involved in primary dysmenorrheal mice with Xiangfu Siwu decoction administration were obtained. Protein ADRM1 may become a target for Xiangfu Siwu decoction.

Light-emitting diode irradiation promotes donor site wound healing of the free gingival graft.

BACKGROUND: This study aims to evaluate the effect of light-emitting diode (LED) light irradiation on the donor wound site of the free gingival graft. METHODS: Rat gingival fibroblasts were chosen to assess the cellular activities and in vitro wound healing with 0 to 20 J/cm(2) LED light irradiation. Seventy-two Sprague-Dawley rats received daily 0, 10 (low-dose [LD]), or 20 (high-dose [HD]) J/cm(2) LED light irradiation on the opened palatal wound and were euthanized after 4 to 28 days; the healing pattern was assessed by histology, histochemistry for collagen deposition, and immunohistochemistry for tumor necrosis factor (TNF)-α infiltration. The wound mRNA levels of heme oxygenase-1 (HO-1), TNF-α, the receptor for advanced glycation end products, vascular endothelial growth factor, periostin, Type I collagen, and fibronectin were also evaluated. RESULTS: Cellular viability and wound closure were significantly promoted, and cytotoxicity was inhibited significantly using 5 J/cm(2) LED light irradiation in vitro. The wound closure, reepithelialization, and collagen deposition were accelerated, and sequestrum formation and inflammatory cell and TNF-α infiltration were significantly reduced in the LD group. HO-1 and TNF-α were significantly upregulated in the HD group, and most of the repair-associated genes were significantly upregulated in both the LD and HD groups at day 7. Persistent RAGE upregulation was noted in both the LD and HD groups until day 14. CONCLUSION: LED light irradiation at 660 nm accelerated palatal wound healing, potentially via reducing reactive oxygen species production, facilitating angiogenesis, and promoting provisional matrix and wound reorganization.

Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: an approach to renoprotection.

Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity.

Adhesion molecules and chemokines: relation to anthropometric, body composition, biochemical and dietary variables / Moléculas de adhesión y quimiocinas; relación con variables antropométricas, de composición corporal, bioquímicas y dietéticas

Introduction: Among the inflammatory mediators involved in the pathogenesis of obesity, the cell adhesion molecules Pselectin, E-selectin, VCAM-1, ICAM-1 and the chemokine MCP-1 stand out. They play a crucial role in adherence of cells to endothelial surfaces, in the integrity of the vascular wall and can be modulated by body composition and dietary pattern. Objectives: To describe and discuss the relation of these cell adhesion molecules and chemokines to anthropometric, body composition, dietary and biochemical markers. Methods: Papers were located using scientific databases by topic searches with no restriction on year of publication. Results: All molecules were associated positively with anthropometric markers, but controversial results were found for ICAM-1 and VCAM-1. Not only obesity, but visceral fat is more strongly correlated with E-selectin and MCP-1 levels. Weight loss influences the reduction in the levels of these molecules, except VCAM-1. The distribution of macronutrients, excessive consumption of saturated and trans fat and a Western dietary pattern are associated with increased levels. The opposite could be observed with supplementation of w-3 fatty acid, healthy dietary pattern, high calcium diet and high dairy intake. Regarding the biochemical parameters, they have inverse relation to HDLC and positive relation to total cholesterol, triglycerides, blood glucose, fasting insulin and insulin resistance. Conclusion: Normal anthropometric indicators, body composition, biochemical parameters and eating pattern positively modulate the subclinical inflammation that results from obesity by reducing the cell adhesion molecules and chemokines (AU)

Introducción: Entre los mediadores inflamatorios involucrados en la fisiopatogenia de la obesidad, se destacan las moléculas de adhesión P-selectina, E-selectina, VCAM-1, ICAM-1 y la quimiocina MCP-1. Estas desempeñan un papel crucial en la adherencia de células en las superficies endoteliales y en la integridad de la pared vascular y pueden ser moduladas por la composición corporal y patrón alimentario. Objetivos: Describir y discutir la relación de esas moléculas de adhesión y quimiocina con marcadores antropométricos, composición corporal, bioquímicas y dietéticas. Métodos: Se utilizaron bases científicas electrónicas para selección de artículos, sin límite de año de publicación. Resultados: Todas las moléculas se asociaron de forma positiva con marcadores antropométricos; sin embargo, se encontraron resultados controvertidos para ICAM-1 y VCAM-1. No solamente la obesidad per si, sino también la grasa visceral está más fuertemente relacionadas con las concentraciones de E-selectina y MCP-1. La pérdida de peso influencia en la reducción de las concentraciones de esas moléculas, con excepción de la VCAM-1. La distribución de macronutrientes, el consumo excesivo de grasa saturada y trans y un patrón alimentario occidental están asociados con aumento de sus concentraciones. El inverso se pudo observar con la suplementación de ácido graso w-3 en la dieta, el patrón alimentario sano y dieta rica en calcio y productos lácteos. Ya en cuanto a los parámetros bioquímicos, las mismas poseen relación inversa con HDL-c y positiva con colesterol total, triacilgliceroles, glicemia e insulinemia de ayuno y resistencia a insulina. Conclusión: Marcadores antropométricos, composición corporal, parámetros bioquímicos y patrón alimentario adecuados modulan positivamente la inflamación subclínica derivada de la obesidad por medio de la reducción de las moléculas de adhesión y quimiocinas (AU)

Carnosic acid reduces cytokine-induced adhesion molecules expression and monocyte adhesion to endothelial cells.

BACKGROUND: Expression of cell adhesion molecules on the endothelium and the attachment of monocytes to endothelium may play a major role in the early atherogenic process. AIM OF THE STUDY: We investigated the effects of carnosic acid on the adhesion of U937 cells to IL-1beta-treated human umbilical vein endothelial cells (HUVECs), as well as on the expression of adhesion molecules. RESULTS: Our data showed that pretreatment with 10 and 20 micromol/l carnosic acid significantly reduced the number of U937 cells adhering to IL-1beta-treated HUVECs. In addition, we found that 20 micromol/l carnosic was more effective than 10 micromol/l carnosic acid at inhibiting expression of cell adhesion molecules (ICAM-1, VCAM-1, and E-selectin), the nuclear translocation of NF-kappaB subunits p65 and p50, and the production of ROS in IL-1beta-stimulated HUVECs. CONCLUSIONS: We conclude that carnosic acid inhibits IL-1beta-induced ICAM-1, VCAM-1 and E-selectin expression in HUVECs through a mechanism that involves NFkappaB. We propose that the reduction in binding of human monocytic cell line U937 to IL-1beta-treated HUVECs is due to the anti-inflammatory properties of carnosic acid.

Minor components of olive oil modulate proatherogenic adhesion molecules involved in endothelial activation.

The Mediterranean diet reduces the risk of coronary artery disease as a consequence of its high content of antioxidants, namely, hydroxytyrosol (HT) and oleuropein aglycone (OleA), typical of virgin olive oil. Because intercellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1) and E-selectin are crucial for endothelial activation, the role of the phenolic extract from extra virgin olive oil (OPE), OleA, HT, and homovanillyl alcohol (HVA) on cell surface and mRNA expression in human umbilical vascular endothelial cells (HUVEC) was evaluated. OPE strongly reduced cell surface expression of ICAM-1 and VCAM-1 at concentrations physiologically relevant (IC50 < 1 microM), linked to a reduction in mRNA levels. OleA and HT were the main components responsible for these effects. HVA inhibited cell surface expression of all the adhesion molecules, whereas the effect on mRNA expression was weaker. These results supply new insights on the protective role of olive oil against vascular risk through the down-regulation of adhesion molecules involved in early atherogenesis.

Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma.

We applied serological analysis of recombinant cDNA expression libraries (SEREX) to cases of esophageal squamous cell carcinoma (SCC) to identify tumor antigens. One of the clones identified was TROP2, which is known as calcium signal transducer. To evaluate the clinical significance of serum anti-TROP2 antibodies (s-TROP2-Abs) in patients with esophageal SCC, the presence of s-TROP2-Abs was analyzed by Western blotting using bacterially expressed TROP2 protein. We found that 23 of 75 (31%) patients were positive for s-TROP2-Abs. Positivity in terms of s-TROP2-Abs showed a significant association with tumor size but not with other clinicopathological features. The protein expression levels of TROP2 were much higher in esophageal SCC cell lines as compared to those in normal esophageal mucosa and its immortalized cells although the mRNA expression levels were not necessarily elevated in malignant cell lines and tissues. Immunohistochemical studies showed that the expression of TROP2 protein in esophageal SCC specimens was noticeably higher than that found in mild hyperplasia of esophageal mucosae. Thus, s-TROP2-Abs seemed useful in the diagnosis of SCC and may be a candidate for serum tumor markers.

The novel coccidian micronemal protein MIC11 undergoes proteolytic maturation by sequential cleavage to remove an internal propeptide.

Host cell invasion is a key step in the life cycle of the intracellular parasite Toxoplasma gondii, the causative agent of toxoplasmosis. Attachment and invasion by this parasite is dependent on secretion of proteins from the micronemes, cigar-shaped organelles found in the apical end of the parasite. Although many of these proteins contain adhesive motifs suggestive of a role in parasite attachment, a growing subset of microneme proteins (MICs) do not possess adhesive sequences implying that they have alternative roles. We have identified a novel 16 kDa microneme protein, TgMIC11, that is conserved among several coccidian parasites. As it traffics through the secretory system, TgMIC11 is modified by two successive proteolytic events to remove an internal propeptide, resulting in the mature protein that consists of an alpha-chain and beta-chain tethered by a single disulfide bond. Dual staining immunofluorescence confirmed that TgMIC11 localises to the apical micronemes and, like other micronemal proteins, it is also secreted in a calcium dependent manner. This is the first microneme protein characterised to date in the phylum Apicomplexa that possesses this unique structure and undergoes maturation by removal of an internal propeptide.

Direct in vivo monitoring of acute allergic reactions in human conjunctiva.

Immediate allergic reactions are initiated by allergen-induced, specific IgE-mediated mast cell degranulation and involve leukocyte recruitment into the inflamed site. We compared conjunctival signs, symptoms, and in vivo leukocyte rolling and extravasation into sites of inflammation in five patients allergic to birch pollen and in 10 nonallergic controls who received a challenge to birch allergen or histamine. Both the specific allergen in allergic patients and histamine, both in patients and in healthy controls, induced symptoms and signs of an immediate allergic reaction together with leukocyte rolling within the conjunctival blood vessels. However, only allergen, not histamine, caused leukocyte extravasation into the site of inflammation in the allergic patients. Allergen also increased expression of endothelial P-selectin in conjunctival vessels and slowed the rolling of leukocytes which is required for their extravasation from blood circulation into the target tissue. Finally, i.v. heparin strongly reduced the number of slowly rolling cells during allergen- or histamine-induced reactions and this can probably hinder the leukocyte extravasation after allergen exposure. These findings suggest that slow rolling is required for leukocyte extravasation in acute allergic reactions, and it can be inhibited by heparin in vivo in therapeutically relevant conditions.

Dendrite-associated opioid-binding cell adhesion molecule localizes at neurosecretory granules in the hypothalamic magnocellular neurons.

Opioid-binding cell adhesion molecule (OBCAM) is a member of the immunoglobulin superfamily containing limbic system-associated membrane protein (IgLON) subgroup of glycosylphosphatidylinositol-anchored immunoglobulin cell adhesion molecules. We have previously found that OBCAM is localized preferentially to dendrites compared with somata and terminals of hypothalamic vasopressin-secreting magnocellular neurons. This localization indicates that OBCAM is one of the dendrite-associated cell adhesion molecules. In the present study, we further characterized the localization and the sorting mechanism, and activity-dependent changes of this molecule in vasopressin-secreting magnocellular dendrites. Confocal microscopic observation revealed the preferential localization of OBCAM at the neurosecretory granules in the vasopressin-positive dendrites. Electron microscopic observation using chromogen-intensified and gold-conjugated methods also demonstrated the OBCAM labeling at most of the neurosecretory granules within the dendrites, while the labeling within the somata was observed at only a few neurosecretory granules. I.c.v. colchicine administration resulted in the disappearance of OBCAM immunoreactivity from the dendrites and in its concomitant accumulation at the somata, suggesting that OBCAM is synthesized at the somata and transported to the dendrites by dendrite-associated neurosecretory granules. During the postnatal development, OBCAM immunoreactivity targeted to vasopressin-positive dendrites became clear from at least 3 weeks after birth, although it appeared at only a few somata 2 weeks after birth. Phosphatidylinositol specific phospholipase C treatment of the membrane fraction of the supraoptic homogenate solubilized OBCAM. Kilon, another IgLON member, was also shown to localize at the neurosecretory granules of vasopressin-positive dendrites via the glycosylphosphatidylinositol anchor. High K(+)-stimulation appeared to cause the diffusion of OBCAM-labeled gold particles from neurosecretory granules together with the exocytosis. These findings indicate that OBCAM is synthesized within the somata, attached to vasopressin neurosecretory granules via the glycosylphosphatidylinositol anchor, and transported to the dendrites. Moreover, the subcellular localization of OBCAM is changed in an activity-dependent manner.

Reduction in homocysteine by n-3 polyunsaturated fatty acids after 1 year in a randomised double-blind study following an acute myocardial infarction: no effect on endothelial adhesion properties.

We hypothesized that n-3 polyunsaturated fatty acids (n-3 PUFAs) as compared to corn oil administered for 1 year following an acute myocardial infarction (MI) may reduce plasma total homocysteine (p-tHcy), ultrasensitive C-reactive protein (microCRP), and the adhesive properties of the endothelium, expressed as soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1). In a prospective, randomised, double-blind study, 300 acute MI patients were allocated to highly concentrated n-3 PUFAs (n = 150) or corn oil (n = 150). After 1 year on treatment there was an intergroup difference in p-tHcy in favour of the n-3 group (n = 118), p = 0.022. However, sE-selectin, sICAM-1 and microCRP were unaffected by the treatment. In conclusion, reduction of p-tHcy by long-term n-3 PUFAs treatment was not associated with demonstrable effects on markers of endothelial adhesion properties.

[The in vivo formation of cementum-like tissue by bovine cementoblasts].

OBJECTIVE: To test the bovine cementoblasts (CBs) cementum-forming ability in vivo. METHODS: Root fragments of newborn bovine freshly extracted mandibular incisor were cultured routinely and 4th-5th passages of CBs were harvested. CBs were then cultured in the medium supplemented with 50 mg/L alpha-ascorbic acid and 10 mmol/l beta-glycerolphosphate to form a thick layer as tissue engineering scaffold for cementum formation. Collagen membrane was used as control scaffold. 2 x 10(6) cells were attached to the CBs-made carrier as well as collagen membrane scaffolds and transplanted subcutaneously into immunodeficient mice. Transplants were harvested at 7th week. Histological sections were stained with HE, alizarin red S and van Kossa methods as well as monoclonal Ab against bovine cementum attachment protein (CAP). RESULTS: CBs-made scaffold supported more cementum-like tissue (CLT) formation than collagen-made scaffold. The CLT formed on CBs scaffold was partly calcified with embedded cells. Uncalcified cementoid-like material could be seen on the surface and was encircled by cubical CB-like cells. The CLT was also positive to CAP and van Kossa staining. CONCLUSIONS: These results suggest that the bovine CBs can form cementum-like tissue. The cell-made carrier is a better scaffold than collagen membrane.

Effects of anti-rheumatic herbal medicines on cellular adhesion molecules.

OBJECTIVE: To test the hypothesis whether herbal medicines ameliorate inflammatory diseases via the modulation of cellular adhesion molecules (CAMs). METHODS: Human neutrophils, synovial fibroblasts, and endothelial cells were incubated with different concentrations of Tripterygium Wilfordii Hook-f (TWH-f) or Tetrandrine in the presence or absence of interleukin 1 (IL1). The amount of soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) secreted by cells were determined by ELISA. The cell surface expression of these three CAMs was detected by flow cytometry. RESULTS: TWH-f at high concentration (50 ng/ml) has a significant (p<0.05) inhibitory effect on both the secretion and the expression of the cellular adhesion molecules. However, Tetrandrine did not demonstrate the same effects. CONCLUSIONS: The cellular adhesion molecules of the endothelium and leucocytes may constitute excellent targets for the development of new anti-inflammation medicines. These results indicate that TWH could be a potential therapeutic agent in the treatment of inflammatory diseases.

High dose supplementation of RRR-alpha-tocopherol decreases cellular hemostasis but accelerates plasmatic coagulation in type 2 diabetes mellitus.

BACKGROUND: Diabetes mellitus is associated with increased generation of free oxygen radicals and depleted scavenging potential (oxidative stress), leading to increased LDL oxidation and platelet hyperreactivity, the major components of atherothrombotic vascular lesions. A main goal of antioxidant therapy is to protect the LDL particle from atherogenic oxidation and to reduce the activated cellular hemostasis. METHODS: We evaluated the influence of a high dose supplementation with 800 IU of the natural antioxidant RRR-alpha-tocopherol (vitamin E) per day for six months on serum levels, vitamin E load of LDL particles (HPLC), lag phase of LDL oxidation (Esterbauer's assay), platelet adhesion molecules, leukocyte-platelet coaggregation (flow cytometry, D-III protocol) and coagulation (INR/PTT) in a group of 36 patients with type 2 diabetes (f/m 22/14; age 58+/-8.0; HbA1 at baseline 10.25+/-1.7). RESULTS: Average vitamin E levels increased 2.65-fold accompanied by a 1.83-fold increase of LDL-associated vitamin E and a 12.3 min prolongation of the lag-phase of LDL oxidation (p<0.001 for all parameters at six months). Platelet expression of PECAM-1 (CD31) (-30.2% positive cells, p<0.001; antigen density -25%, p<0.001), ICAM-2 (CD102) (-2.9% positive cells, p<0.01; antigen density -10.6%, p<0.001) and fibrinogen (-1.6% positive cells, p<0.001; antigen density - 16.1 %, p<0.001) decreased. Concomitantly, platelet-leukocyte-coaggregation increased by 44% (p<0.001), correlating to an INR reduction of 10.4% (1.06+/-0.09 to 0.95+/-0.09, p<0.001, r = - 0.34). The PTT remained constant. CONCLUSION: The antioxidant protection from the increased vitamin E was accompanied by a decreased expression of constitutive and function-dependent platelet adhesion molecules. However, increases in platelet-leukocyte coaggregates and a shortened INR time suggest extrinsic coagulation activation, possibly by induction of a leukocyte tissue factor dependent mechanism. High dose supplements of alpha-tocopherol may override the available redox balance in well controlled type 2 diabetes. However, intrinsic effects of alpha-tocopherol must be discussed.

Human cementum tumor cells have different features from human osteoblastic cells in vitro.

Cells obtained from human cementoblastoma and alveolar bone were isolated and cultured. Initial and late stages of mineralization were assessed by using atomic force microscopy, scanning electron microscopy and X-ray microanalysis. In cultures of cementoblastoma-derived cells the initial stages of mineralization showed well-defined spherical-shaped structures, while the osteoblastic cells showed plaque-like deposits. These morphological patterns of mineral deposition could serve as nucleation centers for hydroxyapatite crystals. Late stages of mineralization at 28 and 35 d maintained those morphological differences established in initial cultures. The material deposited by cementoblastoma and osteoblastic cells, analyzed by EDX spectra, revealed similar Ca/P ratios for both cell types. These values were similar to those reported for hydroxyapatite in enamel and bone. Alkaline phosphatase specific activity (AlP), of osteoblastic cells at 3, 7 and 11 d, showed an increase of 27.9, 50.9 and 37.0% (p < 0.001), respectively. However, at 15 and 19 d there was an increase of AlP activity of cementoblastoma cells by 39.4 and 34.5% over osteoblastic cells (p < 0.001). Immunostaining of cementoblastoma and osteoblastic cells using a specific mAb against a cementum-derived attachment protein revealed strong immunostaining of cementoblastoma cells which was localized to the cell membrane and fibril-like structures (96.2 +/- 1.3). A few osteoblastic cells also stained weakly with the anti-CAP mAb (6.4 +/- 0.6). Sections of decalcified paraffin embedded cementoblastoma specimens, when immunostained with anti-CAP mAb, showed strong immunostaining of the cells surrounding the regular and irregularly-shaped calcified masses of the tumor. Putative cementocytes also stained positively. Immunostaining with a polyclonal antibody against osteopontin strongly stained the osteoblastic cells (89.0 +/- 3.6). Cementoblastoma cells showed weaker staining (54.2 +/- 2.4). The results suggest that cementoblastoma cells could be a major source of specific cementum proteins. These cells could provide the opportunity to elucidate the regulation of the cementogenesis process.

Dynamics of soluble adhesion molecule levels in patients with pollinosis.

OBJECTIVES: To define the dynamics of systemic and local soluble adhesion molecule levels and to discuss the role of these molecules in the pathogenesis of allergic rhinitis. DESIGN: Randomized control trial. SUBJECTS: Twelve volunteers with Japanese cedar pollinosis and 7 healthy volunteers. INTERVENTIONS: The levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble E-selectin, and soluble L-selectin in serum samples and nasal epithelial lining fluids (ELF) from 12 patients with pollinosis were measured 5 times throughout the allergy preseason to postseason, and the results were compared with those from 7 healthy subjects. RESULTS: The levels of sICAM-1 (P < .05) and sVCAM-1 (P < .05) in sera were up-regulated, and the levels of soluble L-selectin (P < .01) in sera were down-regulated during the early stage of the season in the allergic subjects. The difference between the levels of sICAM-1 and sVCAM-1 in sera in the early and mid-season was statistically significant in the allergic subjects (P < .05). The levels of sICAM-1 in ELF were up-regulated during the early and mid-season. The levels of sVCAM-1, soluble E-selectin, and soluble L-selectin in ELF were undetectably low throughout the preseason to postseason. CONCLUSION: There is evidence of the unique stage-dependent differential contributions of various soluble adhesion molecules in the pathogenesis of seasonal allergic rhinitis with a small amount of natural allergen provocation.