Clinical picture of cardiogenic shock as primary manifestation of sepsis originating in the knee joint

This is a case report of a male with infection in the right knee joint progressing to sepsis. However, the patient initially complained mainly of dysarthria and breathlessness. He rapidly developed respiratory insufficiency with the loss of consciousness. Echocardiography revealed severe dysfunction of the left ventricle, suggesting acute failure of the chronically failing heart. The patient was referred to a coronary care unit. Only the further course of the disease, particularly progression of the local finding on the right leg and development of fever, together with significantly elevated inflammatory parameters in laboratory findings, resulted in the diagnosis of sepsis which also included myocardial dysfunction and brain hypoperfusion manifested as dysarthria.     

Association between liver insulin resistance and cardiovascular risk factors

Abstract. Vangipurapu J, Stan?áková A, Kuulasmaa T, Soininen P, Kangas AJ, Ala‐Korpela M, Kuusisto J, Laakso M (University of Eastern Finland and Kuopio University Hospital, Kuopio; University of Oulu and Biocenter Oulu, Oulu, Finland). Association between liver insulin resistance and cardiovascular risk factors. J Intern Med 2012; 272: 402–408. Objectives. The objective of this study was to examine the associations between indices of liver insulin resistance (IR) and whole‐body insulin sensitivity and different cardiovascular disease (CVD) risk factors. Design and subjects. A total of 8750 nondiabetic men (age 57.2 ± 7.1 years, body mass index 26.8 ± 3.8 kg m^?2) were included in this study from the population‐based cross‐sectional Metabolic Syndrome In Men (METSIM) cohort. Liver IR index and Matsuda insulin sensitivity index (ISI) were used as markers of liver IR and whole‐body insulin sensitivity, respectively. Pearson correlation analysis was performed to examine the associations between these indices and various CVD risk factors. Results. Total cholesterol (r = ?0.088 vs. r = 0.020; P < 0.0019), high‐sensitivity C‐reactive protein (CRP) (r = 0.284 vs. r = ?0.219; P < 0.0019) and total triglycerides (r = 0.507 vs. r = ?0.477; P < 0.05) were more highly correlated with liver IR index than with Matsuda ISI. By contrast, Matsuda ISI was nominally more highly correlated with systolic and diastolic blood pressure (r = ?0.234 and r = ?0.275 vs. r = 0.202 and r = 0.239, respectively) compared to liver IR index. Furthermore, the variance explained by liver IR index was larger than that explained by Matsuda ISI for the majority of CVD risk factors measured. Conclusions. Liver IR index correlated more strongly than Matsuda ISI with levels of total cholesterol, CRP and triglycerides. Therefore, liver IR might be a significant indicator of CVD risk amongst men.     

Cytoskeletal changes during development and aging in the cortex of neurofilament light protein knockout mice

The neurofilament light (NFL) subunit is considered as an obligate subunit polymer for neuronal intermediate filaments comprising the neurofilament (NF) triplet proteins. We examined cytoskeletal protein levels in the cerebral cortex of NFL knockout (KO) mice at postnatal day 4 (P4), 5 months, and 12 months of age compared with age‐matched wild‐type (WT) mice of a similar genetic background (C57BL/6). The absence of NFL protein resulted in a significant reduction of phosphorylated and dephosphorylated NFs (NF‐P, NF‐DP), the medium NF subunit (NFM), and the intermediate filament α‐internexin (INT) at P4. At 5 months, NF‐DP, NFM, and INT remained significantly lower in knockouts. At 12 months, NF‐P was again significantly decreased, and INT significantly increased, in KOs compared with wild type. In addition, protein levels of class III neuron‐specific β‐tubulin and microtubule‐associated protein 2 were significantly increased in NFL KO mice at P4, 5 months, and 12 months, whereas β‐actin levels were significantly decreased at P4. Immunocytochemical studies demonstrated that NF‐DP accumulated abnormally in the perikarya of cortical neurons by 5 months of age in NFL KO mice. Neurons that lacked NF triplet proteins, such as calretinin‐immunolabeled nonpyramidal cells, showed no alterations in density or cytoarchitectural distribution in NFL KO mice at 5 months relative to WT mice, although calretinin protein levels were decreased significantly after 12 months in NFL KO mice. These findings suggest that a lack of NFL protein alters the expression of cytoskeletal proteins and disrupts other NF subunits, causing intracellular aggregation but not gross structural changes in cortical neurons or cytoarchitecture. The data also indicate that changes in expression of other cytoskeletal proteins may compensate for decreased NFs. J. Comp. Neurol. 521:1817–1827, 2013. © 2012 Wiley Periodicals, Inc.     

Ciproxifan,an H3 receptor antagonist,improves short-term recognition memory impaired by isoflurane anesthesia

Background

Exposure to volatile anesthetics has been reported to cause temporary or sustained impairments in learning and memory in pre-clinical studies. The selective antagonists of the histamine H3 receptors (H3R) are considered to be a promising group of novel therapeutic agents for the treatment of cognitive disorders. The aim of this study was to evaluate the effect of H3R antagonist ciproxifan on isoflurane-induced deficits in an object recognition task.

Methods

Adult C57BL/6 J mice were exposed to isoflurane (1.3 %) or vehicle gas for 2 h. The object recognition tests were carried at 24 h or 7 days after exposure to anesthesia to exploit the tendency of mice to prefer exploring novel objects in an environment when a familiar object is also present. During the training phase, two identical objects were placed in two defined sites of the chamber. During the test phase, performed 1 or 24 h after the training phase, one of the objects was replaced by a new object with a different shape. The time spent exploring each object was recorded.

Results

A robust deficit in object recognition memory occurred 1 day after exposure to isoflurane anesthesia. Isoflurane-treated mice spent significantly less time exploring a novel object at 1 h but not at 24 h after the training phase. The deficit in short-term memory was reversed by the administration of ciproxifan 30 min before behavioral training.

Conclusion

Isoflurane exposure induces reversible deficits in object recognition memory. Ciproxifan appears to be a potential therapeutic agent for improving post-anesthesia cognitive memory performance.

     

Antibody GD3G7 selected against embryonic glycosaminoglycans defines chondroitin sulfate-E domains highly up-regulated in ovarian cancer and involved in vascular endothelial growth factor binding

Chondroitin sulfate (CS) is abundantly present in the tumor stroma, and tumor-specific CS modifications might be potential targets to influence tumor development. We applied the phage display technology to select antibodies that identify these tumor-specific CS modifications. Antibody GD3G7 was selected against embryonic glycosaminoglycans, and it reacted strongly with CS-E (rich in GlcA-GalNAc4S6S units). In ovarian adenocarcinomas, strong expression of this CS-E epitope was found in the extracellular matrix, and occasionally on tumor cells. No expression was found in normal ovary and cystadenomas. Differential expression was found in ovarian carcinoma cell lines, which correlated with the gene expression of the GalNAc4S-6st enzyme, involved in biosynthesis of CS-E. Vascular endothelial growth factor (VEGF)-sensitive fenestrated (in normal tissues) and tumor blood vessels were both identified by antibody GD3G7, which might implicate a role for CS-E in VEGF biology. VEGF bound to CS-E and antibody GD3G7 could compete for binding of VEGF to CS-E. In conclusion, antibody GD3G7 identified rare CS-E-like structures that were strongly expressed in ovarian adenocarcinomas. This antibody might therefore be instrumental for identifying tumor-related CS alterations.