Oximes as pretreatment before acute exposure to paraoxon

Organophosphates, useful agents as pesticides, also represent a serious danger due to their high acute toxicity. There is indication that oximes, when administered before organophosphate exposure, can protect from these toxic effects. We have tested at equitoxic dosage (25% of LD₀₁) the prophylactic efficacy of five experimental (K‐48, K‐53, K‐74, K‐75, K‐203) and two established oximes (pralidoxime and obidoxime) to protect from mortality induced by the organophosphate paraoxon. Mortalities were quantified by Cox analysis and compared with those observed after pretreatment with a strong acetylcholinesterase inhibitor (10‐methylacridine) and after the FDA‐approved pretreatment compound pyridostigmine. All nine tested substances statistically significantly reduced paraoxon‐induced mortality. Best protection was conferred by the experimental oxime K‐48, reducing the relative risk of death (RR) to 0.10, which was statistically significantly superior to pyridostigmine (RR = 0.31). The other oximes reduced the RR to 0.13 (obidoxime), 0.20 (K‐203), 0.21 (K‐74), 0.24 (K‐75) and 0.26 (pralidoxime), which were significantly more efficacious than 10‐methylacridine (RR = 0.65). These data support the hypothesis that protective efficacy is not primarily due to cholinesterase inhibition and indicate that the tested experimental oximes may be considered promising alternatives to the established pretreatment compound pyridostigmine.     

Abdominelle Sonographie

This review summarizes the current knowledge and possibilities for transabdominal ultrasound techniques in the diagnosis of biliopancreatic diseases. Ultrasound has become widely accepted for the diagnosis of gall bladder diseases as the sensitivity for cholecystolithiasis can be up to 98?% and for bile duct stones it lies between 25?% and 98?% whereas endosonography is more accurate (94–100?%). In the diagnostics of the pancreas ultrasound is the first step in an imaging cascade. In cases of acute pancreatitis the assessment and follow-up of complications (e.g. exsudation, necrosis, pseudocysts, vascular complications and obstructive effects) is particularly valuable. Ductal adenocarcinoma appears to be less vascularized in comparison to the surrounding tissue, while endocrine tumors and some metastases are often hypervascularized. Transabdominal sonography is also helpful in the differentiation of cystic lesions into macrocystic and microcystic adenomas.     

Macrophage p38 mitogen-activated protein kinase activity regulates invariant natural killer T-cell responses during Borrelia burgdorferi infection

The interaction of macrophages with infectious agents leads to the activation of several signaling cascades, including mitogen-activated protein (MAP) kinases, such as p38. We now demonstrate that p38 MAP kinase-mediated responses are critical components to the immune response to Borrelia burgdorferi. The pharmacological and genetic inhibition of p38 MAP kinase activity during infection with the spirochete results in increased carditis. In transgenic mice that express a dominant negative form of p38 MAP kinase specifically in macrophages, production of the invariant natural killer T (iNKT) cell-attracting chemokine MCP-1 and of the antigen-presenting molecule CD1d are significantly reduced. The expression of the transgene therefore results in the deficient infiltration of iNKT cells, their decreased activation, and a diminished production of interferon γ (IFN-γ), leading to increased bacterial burdens and inflammation. These results show that p38 MAP kinase provides critical checkpoints for the protective immune response to the spirochete during infection of the heart.     

Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits

ObjectiveScavenger receptor-class B type I (SR-BI), the receptor for HDL-cholesterol, plays a key role in HDL metabolism, whole body cholesterol homeostasis, and reverse cholesterol transport. We investigated the in vivo impact of hepatic SR-BI inhibition on lipoprotein metabolism and the development of atherosclerosis employing RNA interference.MethodsSmall hairpin RNA plasmid specific for rabbit SR-BI was complexed with galactosylated poly-l-lysine, allowing an organ-selective, receptor-mediated gene transfer. Rabbits were fed a cholesterol-rich diet, and were injected with plasmid-complexes once a week.ResultsAfter 2 weeks of treatment hepatic SR-BI mRNA levels were reduced by 80% accompanied by reduced SR-BI protein levels and a modulation of the lipoprotein profile. Rabbits treated with SR-BI-specific plasmid-complexes displayed higher cholesteryl ester transfer from HDL to apoB-containing lipoproteins, lower HDL-cholesterol, and higher VLDL-cholesterol levels, when compared to controls. In a long-term study, this gene therapeutic intervention led to a similar modulation of the lipoprotein profile, to lower total cholesterol levels, and most importantly to a 50% reduction of the relative atherosclerotic lesion area.ConclusionOur results are another indication that the role of SR-BI in lipoprotein metabolism and atherogenesis in rabbits – a CETP-expressing animal model displaying a manlike lipoprotein profile may be different from the one found in rodents.     

Regression models in periodontal epidemiology: purpose, approach and interpretation

Statistical models, including those using regression analyses, are ubiquitous in periodontal research. However, many investigators may not have a thorough understanding of the concepts underlying the complex statistical models used in much of the current literature. This review aims to demystify biostatical regression models and familiarize the reader with the regression models most commonly encountered in the periodontal literature. Complex models can be intuitively understood in terms of stratified analyses. Therefore, we discuss the use of stratified analyses and emphasize their natural connection to regression models using examples from the periodontal research literature. We critically review various types of regression models, as well as the fundamental assumptions unique to each. An introduction to the fundamentals of model building describes the basics of variable selection procedures and variable management, including discussions regarding the assumptions inherent in common practices. Lastly, modeling approaches to assess confounding and effect modification are discussed by use of examples from the periodontal epidemiological literature.     

Incidence of maxillary sinusitis and oro-antral fistulae in bisphosphonate-related osteonecrosis of the jaw

ObjectiveBisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side-effect of bisphosphonate therapy. In the majority of cases BRONJ occurs in the mandible. As a consequence a detailed investigation of BRONJ of the maxilla and in particular of involvement of the maxillary sinus has largely so far been neglected. The aim of this study was to analyse the frequency of maxillary sinusitis and oro-antral fistulae in BRONJ of the maxilla.Subjects and methodsA retrospective multicentre analysis was carried out in three Departments of Oral and Maxillofacial Surgery focussing on patients suffering from BRONJ in the maxilla. The role of involvement of the maxillary sinus, in particular sinusitis and oro-antral fistula, was analysed.ResultsOut of a total of 170 patients suffering from BRONJ 53 cases (31.2%) with involvement of the maxilla were identified. At least one sign of maxillary sinusitis was present in 43.6% (23/53) and an oro-antral fistula in the course of the disease was detected in 35.8% (19/53) of those patients. The mean length of time of bisphosphonate intake was 36.16 ± 16.32 months. Zoledronate was most frequently associated (60.4%) with symptoms, followed by the combination of Zoledronate/Ibandronate (13.2%), and Zoledronate/Pamidronate or Pamidronate alone (both 7.5%).ConclusionMaxillary sinusitis and oro-antral fistulae are associated with a BRONJ manifestation in the upper jaw in approximately 44%. The involvement of the maxillary sinus should be given special attention and three-dimensional imaging modalities might be necessary, not only to evaluate the extent of necrosis, but also to exclude involvement of the maxillary sinus.     

Traumatische Karotisdissektion

Traumatic dissection of the carotid artery is an easily overlooked consequence of trauma with notable morbidity and mortality which can be observed in up to 4?% of cases involving multiple trauma. Certain mechanisms and patterns of injury as well as specific symptoms should serve as indicators of a dissection and should therefore result in further diagnostic measures. An early diagnosis is of major relevance. This report describes the case of a 45-year-old victim of a traffic accident who showed symptoms of a dissection which had initially not been diagnosed.