Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

Objective: To evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes. Method: This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions. Results: PD was associated with a higher risk of PTB (RRadj. 3.47 95% CI 1.62-7.43), LBW (RRadj. 2.93 95% CI 1.36-6.34) and PROM (RRadj. 2.48 95% CI 1.35-4.56), but not with SGA neonates (RR 2.38 95% CI 0.93 - 6.10). Conclusions: PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women

Evaluation of DNA ploidy in relation with established prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Most patients with ductal pancreatic adenocarcinoma are diagnosed with locally advanced (unresectable) or metastatic disease. The aim of this study was to evaluate the prognostic significance of DNA ploidy in relation with established clinical and laboratory variables in such patients.</p> <p>Methods</p> <p>Two hundred and twenty six patients were studied retrospectively. Twenty two potential prognostic variables (demographics, clinical parameters, biochemical markers, treatment modality) were examined.</p> <p>Results</p> <p>Mean survival time was 38.41 weeks (95% c.i.: 33.17–43.65), median survival 27.00 weeks (95% c.i.: 23.18–30.82). On multivariate analysis, 10 factors had an independent effect on survival: performance status, local extension of tumor, distant metastases, ploidy score, anemia under epoetin therapy, weight loss, pain, steatorrhoea, CEA, and palliative surgery and chemotherapy. Patients managed with palliative surgery and chemotherapy had 6.7 times lower probability of death in comparison with patients without any treatment. Patients with ploidy score > 3.6 had 5.0 times higher probability of death in comparison with patients with ploidy score < 2.2 and these with ploidy score 2.2–3.6 had 6.3 times higher probability of death in comparison with patients with ploidy score < 2.2.</p> <p>Conclusion</p> <p>According to the significance of the examined factor, survival was improved mainly by the combination of surgery and chemotherapy, and the presence of low DNA ploidy score.</p

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

The interplay between lipoproteins, immunity and tryptophan metabolism in atherosclerosis [Elektronisk resurs]

Atherosclerotic cardiovascular disease (CVD) is the leading cause of mortality worldwide. Atherosclerosis is initiated by the infiltration and accumulation of low-density lipoprotein (LDL) cholesterol in the vascular wall, which activates the innate and adaptive arm of immunity, thereby causing chronic vascular inflammation. The LDL particle is immunogenic, as it not only activates lesional macrophages but is also recognized by T cells, and it elicits B cell-mediated antibody responses. Animal immunization studies suggest that anti-LDL antibodies inhibit atherosclerosis, but concerns exist about the potential proinflammatory role of lesional LDL-reactive T cells. In addition to lipoproteins, amino acids and their metabolites can shape immune cell responses, which has been the subject of intense research in the emerging field of immunometabolism. Current clinical practice guidelines on the prevention of CVD focus on controlling traditional risk factors, such as hypercholesterolemia, which indirectly influence inflammation in the vascular wall. Despite optimal management, however, residual inflammatory risk persists and underscores the need for novel therapeutics that directly target vascular inflammation. In Paper I, we generated mouse strains bearing T cell receptor (TCR) transgenic T cells that react to human LDL. Adoptive transfer of these autoreactive T cells or the intercross of TCR transgenic mice with animals expressing human apolipoprotein B-100 (apoB100) on the LDL receptor−/− (LDLR−/−) background led to reduced vascular inflammation and atherosclerosis. Interestingly, a significant proportion of LDL-reactive T cells differentiated into T follicular helper cells, which helped B cells produce anti-LDL antibodies that formed immune complexes with circulating LDL, thereby reducing plasma cholesterol. In Paper II, we employed dendritic cell (DC) based immunotherapy in an attempt to induce apoB100-specific regulatory T (Treg) cells that can exert anti-inflammatory functions in developing plaques. The vaccine was prepared using bone marrow-derived DCs, which were loaded with apoB100 in the presence of the anti-inflammatory cytokine transforming growth factor beta 2 (TGF-β2). Immunotherapy with these DCs promoted an immune response to apoB100 that favoured the accumulation of Treg cells in atherosclerotic plaques, increased vascular expression of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO1), and ameliorated atherosclerosis. In vitro experiments suggested that the Treg molecule cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) regulates IDO1 expression in macrophages and vascular cells. In Paper III, we studied the role of IDO1-mediated tryptophan metabolism in atherosclerosis using an inhibitor of IDO1 enzyme, 1-methyl-tryptophan. In vivo and in vitro data indicated that IDO1 regulates vascular inflammation, particularly in smooth muscle cells, and inhibits atherosclerosis possibly via the generation of the metabolite 3-hydroxyanthranilic acid (3-HAA). In Paper IV, we investigated the effects of increased endogenous 3-HAA levels on plasma lipids and atherosclerosis using an inhibitor of the enzyme 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO). Our data suggested that 3-HAA can lower plasma lipids via inhibition of the sterol regulatory element binding protein-2 (SREBP-2) pathway in hepatocytes and suppress inflammation via inhibition of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. The studies included in the present thesis illustrate the intricate interplay between metabolism and immunity in atherosclerosis. It is my belief that our findings will contribute to the development of effective immunomodulatory strategies directly targeting vascular inflammation and addressing the residual inflammatory cardiovascular risk

Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab

Athanasios D Anastasilakis,1 Konstantinos A Toulis,1 Stergios A Polyzos,2 Chrysostomos D Anastasilakis,3 Polyzois Makras41Department of Endocrinology, 424 General Military Hospital, 2Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, 3Department of Pharmacology, 424 General Military Hospital, Thessaloniki; 4Department of Endocrinology and Diabetes, 251 Hellenic Air Force and VA General Hospital, Athens, GreeceAbstract: Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-&amp;kappa;B ligand (RANKL), a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. Denosumab treatment is associated with a rapid, sustained, and reversible reduction in bone turnover markers, a continuous marked increase in bone mineral density at all sites, and a marked decrease in the risk of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis. Therefore, it could be considered as an effective alternative to previous bisphosphonate treatment as well as first-line treatment of severe osteoporosis. Cost-effectiveness studies support this suggestion. In addition, denosumab seems to be the safest treatment option in patients with impaired renal function. Denosumab is characterized by reversibility of its effect after treatment discontinuation, in contrast with bisphosphonates. Large-scale clinical trials, including the extension of FREEDOM trial for up to 5 years, are reassuring for its safety. However, given its brief post-market period, vigilance regarding adverse events related to putative RANKL inhibition in tissues other than bone, as well as those related to bone turnover oversuppression, is advised.Keywords: adverse event, denosumab, efficacy, fracture, osteoporosis, safet