The Biomechanical Investigation of Osseointegration Levels in Titanium Implants Simultaniously Placed with Different Bone Grafts.

BACKGROUND: Dental implant-supported prostheses have been scientifically accepted and have been a common treatment choice in the case reconstructing of partial or total tooth loss. In additon, bone grafts (alloplast, xsenograft, allograft) are frequently used in implant and sinus lift surgical procedures. AIM: The aim of this study is to investigate the bone-implant osseointegration levels of titanium implants simultaniously placed with different bone grafts. MATERIALS AND METHODS: In the study, 32 female S. Dawley rats were divided into four groups. In the control group (n = 8), turned surface implants with a 2.5 mm diameter and a 4 mm length were placed in the tibia of the rats without the use of a graft material. In the experimental groups, bone cavities were opened in the tibias of the rats and a synthetic (alloplast) graft (n = 8), human allograft (n = 8), and bovine xsenograft (n = 8) were placed simultaniously with a 2.5 mm diameter and a 4 mm length turned surface titanium implants. The cavities in the experimental groups were opened with a 4 mm diameter and a 5 mm length. After 8 weeks of recovery, all rats were sacrificed at the end of the experimental period. The implants and surrounding bone tissue were removed. The removed tissue was subjected to biomechanical analysis in order to evaluate bone-implant osseointegration and peri-implant new bone formation. The Kolmogorov-Smirnov test, Kruskal-Wallis test, and Mann-Whitney U-test were used in the study. Significance was evaluated at the P < 0.05 level. RESULTS: In the biomechanical analyses, it was determined that there was no statistically significant difference between the control group and the other three groups in which different graft materials were applied in terms of bone-implant osseointegration (P > 0.05). In other words, in the biomechanical analyses, no statistical difference was found between any of the groups. CONCLUSIONS: As a result of this study, it can be thought that different graft materials can be successfully used in peri-implant-guided bone regeneration and may be an alternative to autogenous grafts.

The Investigation of Bone-Implant Connection and New Bone Formation in Fasting and High-Fatty Diet Rats.

BACKGROUND: Hyperlipidemia caused by a high-fat diet (HFD) has many adverse effects on the cardiovascular system, including vascular problems. In addition, a HFD also has significant adverse effects on bone health. AIM: The aim of this study is to examine bone-implant osteointegration and new bone formation in peri-implant defects in fasting and high-fatty diet applied rats. MATERIALS AND METHODS: In this study, 28 female Sprague Dawley rats were used. The rats were divided into four groups, with seven rats in each group: the control group on a normal diet (Group 1) (n = 7), the fasted group (Group 2) (n = 7), the high-fatty diet (HFD) group (Group 3) (n = 7), and the fasted and HFD group (Group 4) (n = 7). Titanium implants with a diameter of 2.5 mm and a length of 4 mm were placed in the right tibia bones of the subjects, and a bone graft corresponding to 2 mm of the implant length was placed in the bone defect applied to the neck region. All rats that continued the administered diet for 12 weeks were sacrificed at the end of the experiment period. The implants and surrounding bone tissue were surgically removed and subjected to biomechanical analysis to assess bone-implant osteointegration and peri-implant new bone formation. RESULTS: It was determined that there was no statistically significant difference between the rats in the control group and the other three groups in terms of bone-implant osteointegration and peri-implant new bone formation (P > 0.05). CONCLUSION: As a result of this study, it was determined that fasting or maintaining a HFD does not adversely affect bone-implant osteointegration or peri-implant new bone formation in the tibias of rats.

Protein kinase C-delta (PKCδ), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice.

This corrects the article DOI: 10.1038/mi.2017.68.

Protein kinase C-delta (PKCδ), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice.

We previously demonstrated that protein kinase C-δ (PKCδ) is critical for immunity against Listeria monocytogenes, Leishmania major, and Candida albicans infection in mice. However, the functional relevance of PKCδ during Mycobacterium tuberculosis (Mtb) infection is unknown. PKCδ was significantly upregulated in whole blood of patients with active tuberculosis (TB) disease. Lung proteomics further revealed that PKCδ was highly abundant in the necrotic and cavitory regions of TB granulomas in multidrug-resistant human participants. In murine Mtb infection studies, PKCδ-/- mice were highly susceptible to tuberculosis with increased mortality, weight loss, exacerbated lung pathology, uncontrolled proinflammatory cytokine responses, and increased mycobacterial burdens. Moreover, these mice displayed a significant reduction in alveolar macrophages, dendritic cells, and decreased accumulation of lipid bodies (lungs and macrophages) and serum fatty acids. Furthermore, a peptide inhibitor of PKCδ in wild-type mice mirrored lung inflammation identical to infected PKCδ-/- mice. Mechanistically, increased bacterial growth in macrophages from PKCδ-/- mice was associated with a decline in killing effector functions independent of phagosome maturation and autophagy. Taken together, these data suggest that PKCδ is a marker of inflammation during active TB disease in humans and required for optimal macrophage killing effector functions and host protection during Mtb infection in mice.

Monitoring the effects of water pollution on Cyprinus carpio in Karakaya Dam Lake, Turkey.

Karakaya Dam Lake (KDL) is one of the most important water sources, both for irrigation and fishery, located in eastern part of Turkey. This study is concerned with the pollution of the lake contributed by urban, industrial and agricultural activities. The parameters selected for this aim were the enzymes commonly used as biomarkers of environmental pollution. The activity of glutathione S-transferase (GST), carboxylesterase (CE), lactate dehydrogenase (LDH), acid phosphatase (ACP) and aspartate amino transferase (AST) has been determined in liver tissue samples of Cyprinus carpio, a representative species of KDL. Furthermore, brain acetylcholinesterase (AChE) activity which is mainly affected by pesticides such as organophosphates, has been assayed. Chemical analysis results showed that KDL was polluted by various heavy metals as it was apparent from water, sediment and gill tissue. The activity of brain AChE was significantly lower in all localities than Tecimli area (St-5) where there is no agricultural and industrial activities in the immediate periphery. Thus, this change of AChE activity may relate to agricultural pollution in KDL. On the other hand, no significant differences were found for selected enzyme biomarkers, but condition factor (CF) or hepatosomatic index were significantly different from the St-5 samples, a result that may be attributed to water pollution in KDL by various contaminants.

Long-term neurological outcome of acute encephalitis.

To understand the viral etiology of acute childhood encephalitis in Elazig, Eastern Turkey, 36 children aged between 4 months and 14 years who were treated in a regional medical center between January 1995 and June 1999 were studied. Viral etiology was identified in 16 of 34 (47.1 per cent) cases and the most frequently detected pathogens was mumps (seven cases, 20.6 per cent). No specific etiology was found in 18 (52.9 per cent) cases. Among the survivors, mental and/or focal neurological deficits persisted in 18 (52.9 per cent). Two children died and 32 survived, of whom 16 were left with no neurological sequel, 10 had persistent neurological sequel, and eight recovered with some degree of handicap. Improvement in the general health and sanitation of the population, and the universal use and development of new vaccination will significantly reduce the incidence of viral encephalitis.

Re-expression of estrogen receptor alpha in estrogen receptor alpha-negative MCF-7 cells restores both estrogen and insulin-like growth factor-mediated signaling and growth.

Estrogen can increase insulin-like growth factor-I receptor (IGF-IR) and insulin receptor substrate-1 (IRS-1) expression, two key components of IGF-I-mediated signaling. The result is sensitization of breast cancer cells to IGF-I and synergistic growth in the presence of estrogen and IGF-I. We hypothesized that loss of estrogen receptor alpha (ERalpha) would result in reduced IGF-mediated signaling and growth. To test this hypothesis, we examined IGF-I effects in MCF-7 breast cancer cell sublines that have been selected for loss of ERalpha (C4 and C4-12 cells are ERalpha-negative) by long-term estrogen withdrawal. C4 and C4-12 cells had reduced IGF-IR and IRS-1 mRNA and protein expression (compared with MCF-7 cells) that was not inducible by estrogen. Furthermore, C4 and C4-12 cells showed reduced IGF-I signaling and failed to show any growth response to either estrogen or IGF-I. To prove that loss of IGF and estrogen-mediated signaling and growth was a consequence of loss of ERalpha, we re-expressed ERalpha in C4-12 cells by stable transfection with HA-tagged ERalpha. Three independent C4-12 ERalpha-HA clones expressed a functional ERalpha that (a) was down-regulated by estrogen, (b) conferred estrogen-induction of cyclin D1 expression, and (c) caused estrogen-mediated increase in the number of cells in S phase. All of the effects were completely blocked by antiestrogens. Interestingly, ERalpha-HA expression in C4-12 cells did not restore estrogen induction of progesterone receptor expression. However, ERalpha-positive C4-12 cells now exhibited estrogen-induction of IGF-IR and IRS-1 levels and responded mitogenically to both estrogen and IGF-I. These data show that ERalpha is a critical requirement for IGF signaling, and to our knowledge this is the first report of functional ERalpha expression that confers estrogen-mediated growth of an ER-negative breast cancer cell line.

Differential effects of TNF and LTalpha in the host defense against M. bovis BCG.

Signaling via TNF receptor type 1 (TNFR1) was shown to be crucial in host defense against the intracellular pathogens L. monocytogenes, M. tuberculosis and M. bovis. To investigate the function of TNF and LTalpha in host defense against M. bovis, mice double deficient for TNF and LTalpha (TNF / LTalpha (- / -)), TNF / LTalpha (- / -) mice complemented with a murine LTalpha transgene (TNF(- / -)) and LTalpha (- / -) mice were infected with BCG and the ensuing pathology was investigated. Control mice showed a normal host defense with early clearance of bacteria. The granulomatous reaction in the liver was accompanied by recruitment of activated macrophages characterized by their acid phosphatase positivity and differentiation into epithelioid cells as well as a coordinated expression of proinflammatory transcripts. In contrast, TNF / LTalpha (- / -) mice showed no comparable recruitment of activated macrophages in the liver. Furthermore, these mice showed extensive necrotic pulmonary lesions with massive growth of acid fast bacilli. Reintroduction of LTalpha as a transgene into TNF / LTalpha (- / -) mice prolonged survival but did not restore resistance to BCG. This, at least partially protective role of LTalpha was further supported by data demonstrating that LTalpha -deficient mice as well were susceptible to BCG infection. In contrast to the deleterious effect of TNF / LTalpha deficiency in BCG infection, BCG-infected TNF / LTalpha (- / -) mice were tolerant to LPS-induced shock. These results demonstrate that TNF as well as LTalpha are involved in murine host defense against BCG and that absence of TNF / LTalpha protects BCG-infected mice from LPS mediated shock.

Lethal Mycobacterium bovis Bacillus Calmette Guérin infection in nitric oxide synthase 2-deficient mice: cell-mediated immunity requires nitric oxide synthase 2.

The role of nitric oxide (NO) in Mycobacterium bovis Bacillus Calmette Guerin (BCG) infection was investigated using nitric oxide synthase 2 (nos2)-deficient mice, because NO plays a pivotal protective role in M. tuberculosis infection. We demonstrate that nos2-deficient mice were unable to eliminate BCG and succumbed within 8 to 12 weeks to BCG infection (10(6) CFU) with cachexia and pneumonia, whereas all infected wild-type mice survived. The greatest mycobacterial loads were observed in lung and spleen. Nos2-deficient mice developed large granulomas consisting of macrophages and activated T cells and caseous necrotic lesions in spleen. The macrophages in granulomas from nos2-deficient mice had reduced acid phosphatase activities, suggesting that NO is required for macrophage activation. The absence of NOS2 affected the cytokine production of the Th1 type of immune response, except IL-18. Serum amounts of IL-12p40 were increased and IFN-gamma was decreased compared with wild-type mice. The lack of NOS2 resulted in an overproduction of TNF, observed throughout the infection period. Additionally, TNFR1 and TNFR2 shedding was altered compared with wild-type mice. Up-regulation of TNF may be compensatory for the lack of NOS2. The late neutralization of TNF by soluble TNF receptors resulted in heightened disease severity and accelerated death in nos2-deficient mice but had no effect in wild-type mice. In conclusion, the inability of nos2-deficient mice to kill M. bovis BCG resulted in an accumulation of mycobacteria with a dramatic activation of the immune system and overproduction of pro-inflammatory cytokines, which resulted in death.

Insulin-like growth factor I-induced degradation of insulin receptor substrate 1 is mediated by the 26S proteasome and blocked by phosphatidylinositol 3'-kinase inhibition.

Insulin receptor substrate 1 (IRS-1) is a critical adapter protein involved in both insulin and insulin-like growth factor (IGF) signaling. Due to the fact that alteration of IRS-1 levels can affect the sensitivity and response to both insulin and IGF-I, we examined the ability of each of these ligands to affect IRS-1 expression. IGF-I (10 nM) stimulation of MCF-7 breast cancer cells caused a transient tyrosine phosphorylation of IRS-1 that was maximal at 15 min and decreased thereafter. The decrease in tyrosine phosphorylation of IRS-1 was paralleled by an apparent decrease in IRS-1 levels. The IGF-mediated decrease in IRS-1 expression was posttranscriptional and due to a decrease in the half-life of the IRS-1 protein. Insulin (10 nM) caused tyrosine phosphorylation of IRS-1 but not degradation, whereas high concentrations of insulin (10 microM) resulted in degradation of IRS-1. IGF-I (10 nM) stimulation resulted in transient IRS-1 phosphorylation and extracellular signal-related kinase (ERK) activation. In contrast, insulin (10 nM) caused sustained IRS-1 phosphorylation and ERK activation. Inhibition of 26S proteasome activity by the use of lactacystin or MG132 completely blocked IGF-mediated degradation of IRS-1. Furthermore, coimmunoprecipitation experiments showed an association between ubiquitin and IRS-1 that was increased by treatment of cells with IGF-I. Finally, IGF-mediated degradation of IRS-1 was blocked by inhibition of phosphatidylinositol 3'-kinase activity but was not affected by inhibition of ERK, suggesting that this may represent a direct negative-feedback mechanism resulting from downstream IRS-1 signaling. We conclude that IGF-I can cause ligand-mediated degradation of IRS-1 via the ubiquitin-mediated 26S proteasome and a phosphatidylinositol 3'-kinase-dependent mechanism and that control of degradation may have profound effects on downstream activation of signaling pathways.

A role for lymphotoxin beta receptor in host defense against Mycobacterium bovis BCG infection.

To investigate the role of membrane lymphotoxin (LT)alpha1 / beta2 and its LTbeta receptor (LTbetaR) in the protective immune response to Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection, we have used a soluble fusion molecule (LTbetaR-IgG1). LTbetaR-Ig treatment interferes with granuloma formation mainly in the spleen by inhibiting macrophage activation and nitric oxide synthase activity. In addition, a large accumulation of eosinophils was observed in the spleen of LTbetaR-Ig-treated infected mice. Decreased blood levels of IFN-gamma and increased IL-4 were also observed, suggesting that the LTbetaR pathway is important in BCG infection to favor a Th1 type of immune response. The treatment of transgenic mice expressing high blood levels of a soluble TNFR1-IgG3 fusion protein with LTbetaR-Ig resulted in a still higher sensitivity to BCG infection, and extensive necrosis in the spleen. In conclusion, these results suggest that the LTbetaR and the TNFR pathways are not redundant in the course of BCG infection and protective granuloma formation: the LTbetaR pathway appears to be important in spleen granuloma formation, whereas the TNFR pathway has a predominant role in other tissues.

Measurement of blood flow by the 133Xe clearance technique to grafts of amnion used in vestibuloplasty.

The purpose of this study was to determine the blood supply to lyophilized amniotic membranes when used as graft material in vestibuloplasties. 133Xe clearance technique was used to measure the blood flow to the grafts. A total of 20 patients had either Clark (10) or Kazanjian (10) vestibuloplasties. The blood flow was determined at 2-3 days preoperatively and at 10 and 30 days postoperatively. The preoperative mandibular anterior alveolar mucosal blood flow was 34.4 +/- 10.7 and 23.1 +/- 13.1 ml/100 g/min for the Clark and Kazanjian groups, respectively. Ten days after vestibuloplasty operation with lyophilized amniotic membrane graft application the blood flow to the graft increased to 56.8 +/- 45.4 and 62.6 +/- 30.4 ml/100 g/min for the Clark and Kazanjian groups, respectively. The corresponding values at 30 days postoperatively were 24.6 +/- 10.2 and 22.2 +/- 9.2 ml/100 g/min, indicating the return to normal levels. The changes in blood flow as a function of time were statistically significant in each group (P<0.05). Our results demonstrated the angiogenic effect of lyophilized amniotic membranes until mucoid degeneration after 10-15 days.