Clinical safety of enamel matrix derivative (EMDOGAIN®) in the treatment of periodontal defects

Abstract The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN® in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN® in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN® at I comparable site. In total 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery. 56 other samples were taken after one treatment with EMDOGAIN®, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN® is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of post-surgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months post surgery. and this difference had increased further at the 3 year follow-up. The 2.5–3 mm increase in attachment and bone level after treatment with EMDOGAIN® was of the same magnitude as seen in the studies with split-mouth design aiming for lest of effectiveness of EMDOGAIN®.     

Lipid extract from completely sporoderm‐broken germinating Ganoderma sinensis spores elicits potent antitumor immune responses in human macrophages

Ganoderma sinensis has been used widely in Oriental countries for the prevention and treatment of various diseases including cancer. Previous studies have shown that the lipid extract from Ganoderma exhibits direct cytotoxicity against tumor cells. Here, it is reported that the lipid extract from germinating G. sinensis spores, at lower concentrations that have no direct tumoricidal activity, induce potent antitumor immune responses in human monocytes/macrophages. Upon stimulation with the lipid extract, monocytes/macrophages exhibited markedly increased production of proinflammatory cytokines and surface expression of costimulatory molecules. Conditioned medium from stimulated cells effectively suppressed the growth of tumor cells. Apparently, the lipid extract triggered macrophage activation via a mechanism different from that associated with LPS. Moreover, it was observed that the lipid extract could partially re‐establish the antitumor activity of the immunosuppressive tumor‐associated macrophages. These results indicated that in addition to its direct tumoricidal activity, the lipid extract from G. sinensis spores could exert antitumor activity by stimulating the activation of human monocytes/macrophages. Copyright © 2008 John Wiley & Sons, Ltd.     

Improved long-term bone-implant integration Experiments in transgenic mice overexpressing bovine growth hormone

Several recent studies have investigated the effects of growth hormone (GH) on the healing of fractures and bone ingrowth, but with conflicting results. The negative results may be due to antibody formation against injected GH or because some experimental models are able to prove only positive GH effects. In this study, we wanted to investigate the effect of GH on implant integration in bone. To avoid potential formation of antibodies against injected GH, we used a model with transgenic mice overexpressing bovine GH (bGH).

Titanium implants were inserted in the forehead of the mice. 4 months after insertion, the implants were cut out en bloc with the surrounding bone. The calcified specimens were cut and ground to a thickness of approximately 10m. Histomorphometry demonstrated significantly more direct bone-to-metal contact in the transgenic mice than in the nontransgenic littermates. Our findings indicate that systemic administration of GH in humans may improve implant integration in bone.     

Increase in rat brain glutathione following intracerebroventricular administration of gamma-glutamylcysteine.

The effects of intracerebroventricularly (i.c.v.) administered gamma-glutamylcysteine (gamma-GC) and glutathione (GSH) monoethyl ester, subcutaneously (s.c.) injected L-2-oxo-4-thiazolidinecarboxylic acid (OTC) and intraperitoneally (i.p.) administered cysteine on the concentration of GSH in rat brain were investigated. The brain content of GSH, cysteine and gamma-GC was determined by HPLC with electrochemical detection (gold/mercury electrode) using N-acetylcysteine as internal standard. A dose-dependent increase in the GSH concentration (145-170% of controls) was found in the substantia nigra (SN) and in the rest of the brain stem after injection of gamma-GC, whereas no significant alterations in GSH were observed in the striatum and in the cerebral cortex. High levels of gamma-GC could be detected in the brain tissue after the administration, and the concentration of cysteine did also increase markedly after gamma-GC injection in all brain regions assessed. I.c.v. administration of L-buthionine sulfoximine (L-BSO) reduced the brain concentration of GSH by 50-70% within 24 hr. Injection of gamma-GC 24 hr after L-BSO resulted in an increase in GSH up to control values within 1-3 hr in the SN and the rest of the brain stem, whereas only a slight increase in GSH was observed in the striatum and the cerebral cortex. The concentration of GSH in the striatum and SN did not change after i.p. injection of cysteine, but a slight increase in the GSH concentration in the limbic region was observed. GSH monoethyl ester (i.c.v.) and OTC (s.c.) did not produce any significant increase in the GSH concentration in the brain. When the GSH concentration had been reduced by administration of L-BSO (i.c.v.; 24 hr) subsequent injection of GSH monoethyl ester led to a slight increase in the striatal and limbic GSH levels. These data show that, of the drugs studied, gamma-GC was the most effective in increasing brain GSH. It could thus serve as a valuable tool in future studies regarding metabolism and function of GSH in the brain. The observed difference in the effects of gamma-GC in different brain regions indicate that the brain tissue is not homogeneous with regard to GSH synthesizing capacity.     

Functional analysis of rabbit anti-peptide antibodies which mimic autoantibodies against the beta 1-adrenergic receptor in patients with idiopathic dilated cardiomyopathy.

A synthetic peptide corresponding to the second extracellular loop of the beta 1-adrenergic receptor was used as an antigen for antibody production in three rabbits. Antibodies of high titers were obtained in all rabbits. Only one rabbit yielded antibodies which decreased radioligand binding on the receptor in a similar way to that described for autoantibodies in patients with dilated cardiomyopathy. These antibodies recognized the receptor protein in immunoblots. Epitope mapping indicated that the N-terminal sequence of the loop used as antigen was the target of the major antigen fraction. Incubation of antibodies with C6 glioma cell membranes or inner membranes of E. coli, which express the human beta 1-adrenergic receptor, resulted in a decrease in number of radioligand binding sites. This decrease was dependent on the concentration of antibody and of Mg++ ions. It was not affected by the GTP analog GppNHp or the beta 1 subtype-specific antagonist metoprolol. The agonist, isoproterenol, also induced a decrease but the effects of antibody and agonist were not additive. These results suggest that the antibodies induce a Mg(++)-dependent, 'active', labile conformation of the receptor, independent from coupling to the GTP regulatory protein, but similar to that induced by the agonist isoproterenol. This interpretation was corroborated by the beta 1-adrenergic receptor agonist-like effect of the antibodies on cardiomyocytes in culture.     

Predictive power of various models for longitudinal attachment level change

Abstract Several statistical models that have been suggested in the periodontal literature for describing longitudinal attachment level changes, such as the gradual loss, single-burst, multiple-burst, and random walk models as well as other models introduced in this paper are compared by their power to predict future attachment loss. The data used in this analysis is from 1061 sites of 8 subjects, with moderate to severe periodontal disease, monitored monthly for about a year. This study found that none of the suggested models could significantly outperform the naive mean predictor, which predicts the future attachment level from the past mean. It was also found that no single model, such as the burst, gradual, or random walk, together with measurement error can fully explain the variation in the data. These results indicate that in the course of one year, the attachment level change may not follow the same model. Consequently, a model that fits well to past data cannot be accurately extended to the future.     

Legionnaires' Disease in Leukaemic Reticuloendotheliosis

At our hospital 15 cases of leukaemic reticuloendotheliosis and 4 cases of Legionnaires' disease have been diagnosed. 3 patients had both diseases. The clinical findings are reported. It is probable that patients with leukaemic reticuloendotheliosis have an increased susceptibility to Legionnaires' disease. Possible reasons for the decreased resistance are discussed.