Maresin 1 attenuates pro-inflammatory activation induced by β-amyloid and stimulates its uptake

Alzheimer's disease (AD) is the most common dementia, characterized by pathological accumulation of β-amyloid (Aβ) and hyperphosphorylation of tau protein, together with a damaging chronic inflammation. The lack of effective treatments urgently warrants new therapeutic strategies. Resolution of inflammation, associated with beneficial and regenerative activities, is mediated by specialized pro-resolving lipid mediators (SPMs) including maresin 1 (MaR1). Decreased levels of MaR1 have been observed in AD brains. However, the pro-resolving role of MaR1 in AD has not been fully investigated. In the present study, human monocyte-derived microglia (MdM) and a differentiated human monocyte cell line (THP-1 cells) exposed to Aβ were used as models of AD neuroinflammation. We have studied the potential of MaR1 to inhibit pro-inflammatory activation of Aβ and assessed its ability to stimulate phagocytosis of Aβ₄₂. MaR1 inhibited the Aβ₄₂-induced increase in cytokine secretion and stimulated the uptake of Aβ₄₂ in both MdM and differentiated THP-1 cells. MaR1 was also found to decrease chemokine secretion and reduce the associated increase in the activation marker CD40. Activation of kinases involved in transduction of inflammation was not affected by MaR1, but the activity of nuclear factor (NF)-κB was decreased. Our data show that MaR1 exerts effects that indicate a pro-resolving role in the context of AD and thus presents itself as a potential therapeutic target for AD.     

The novel relationship between Sirt3 and autophagy in myocardial ischemia–reperfusion

Class III histone deacetylases (HDACs) belong to the proteasome family, comprising seven family members identified in mammalian cells, identified Sirt1–Sirt7. As an important member of HDACs, Sirt3 is hotly debated for its multiple functions. It was reported that Sirt3 got involved in the alleviation of multiple diseases, including myocardial infarction, neuron ischemia, hypertrophy, and diabetic myopathy. Through regulating many cellular mechanisms, such as apoptosis, autophagy, and clearance of reactive oxygen species (ROS), Sirt3 played an important role in the alleviation of myocardial ischemia–reperfusion injury. Nowadays Sirt3-induced autophagy was indicated to be involved in the process of the development of myocardial ischemia–reperfusion injury. Sirt3 could both activate and inhibit autophagy process by activating different downstream signal pathways, such as Sirt3–AMP-activated protein kinase pathway, Sirt3–Foxo3a pathway, and Sirt3–superoxide dismutase–mitochondrial ROS pathway. Whereas the Sirt3-induced autophagy in different phases of myocardial ischemia–reperfusion has not been systematically illustrated. In this review, we summarized the regulated mechanisms found in these years and listed the updated research about the relationship between Sirt3 and autophagy which are both positive and negative during myocardial ischemia–reperfusion phase. We anticipated that we may controlled the activation of autophagy by regulating the concentration of Sirt3 in myocyte. By maintaining a proper expression of autophagy in different phases of myocardial ischemia–reperfusion, we could reduce the morbidity of patients with myocardial infarction apparently in the future.     

Mycetoma of the forearm due to Actinomadura madurae

A case of mycetoma, with abscess-like lesions which appeared on the right forearm of a 43-year-old male, is briefly reported. A few whitish granules were detected in the oily-like discharge, the same as in the histologic examination. No bone involvement was discovered in X-ray examination. Actinomadura was identified in the culture. A daily dose of 4 g bactrin brought significant improvement to the patients continuing the treatment.     

The effects of parathyroid hormone-related peptide on cardiac angiogenesis,apoptosis, and function in mice with myocardial infarction

It is known that parathyroid hormone-related peptide (PTHrP) contains a nuclear localization sequence (NLS, 87-107), which, together with its C-terminus (107-139), has been shown to positively regulate vascular smooth muscle cell (VSMCs) proliferation and vascular neointima formation, and inhibit cellular apoptosis. The role of PTHrP in ischemic cardiac diseases remains unclear. In this study, we attempted to determine whether PTHrP 87 to 139 can play a role in promoting cardiac function via enhancing angiogenesis after myocardial infarction (MI) occurred. MI was reproduced in C57BL/6 mice using a coronary artery ligation method. In total, three groups (n = 11 per group) of animals were used, and they were received either PTHrP 87 to 139 (80 µg/kg, treatment group) or saline (MI and Sham group) subcutaneously once a day for 4 weeks after MI. To measure cardiac function, an echocardiography was generated and cardiac tissue was harvested for immunohistological studies 4 weeks after operation. Our results show that, after MI, the cardiac function of the experimental mice was significantly impaired. PTHrP 87 to 139 treatment attenuated cardiac dysfunction in MI mice. Besides, as indicated by decreased heart weight/body weight and lung weight/body weight ratio, PTHrP 87 to 139 attenuated pulmonary congestion and cardiac hypertrophy. Masson staining revealed that PTHrP 87 to 139 attenuated myocardial fibrosis after MI. Also, terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining and the expression of cleaved caspase 3 suggested that MI-induced myocytes apotosis was inhibited by PTHrP 87 to 139. In addition to the significantly increased capillary density, PTHrP 87 to 139 treatment also induced p-Akt and several angiogenic factors. In conclusion, PTHrP 87 to 139 treatment preserved cardiac function after MI, and stimulated angiogenesis via upregulating vascular endothelial growth factor and basic fibroblast growth factor (bFGF) in infarct border zone of ischemic myocardium,. These results suggest that PTHrP 87 to 139 is of therapeutic potential for MI.     

Quantitative Assessment of Polyethylene Component Position in a Mobile-Bearing Prosthetic Knee,Using a Single Radiograph

Rationale and Objectives. To reduce tibio-femoral misalignment, the polyethylene bearing-component of a new knee prosthesis was allowed limited motion on the underlying metallic component. The object of the work presented here was to develop a suitable radiographic technique for quantifying the in-vivo position of the bearing. By collecting these data at discrete flexion angles, the functional operation of the prosthesis could be determined

Methods. The known geometries between landmarks on the two components were used to produce algorithms for reconstructing their spatial positions from a single radiograph. A custom-designed computer program utilized these algorithms to determine the relative translation and rotation of the polyethylene component

Results. This technique produced typical errors of 0.54 mm translation and 0.56° rotation between the polyethylene component and the underlying metallic component

Conclusions. A practical method has been developed for assessing mobile-bearing motion, in vivo. This method can be applied to other prosthetic devices, or combinations of components, once the requirement for identifiable landmarks has been addressedClinical Relevance. Skeletal and soft-tissue changes in the pathological knee may produce abnormal rotations and translations in the transverse tibial plane. This technique is intended both to validate the design philosophy of a mobile-bearing prosthesis and to provide additional data on any pathological motions, which will have implications for future prosthetic designs.     

Preface

"Although few people die of pain,many people die in pain and even more live in pain"——IASP On October11,2004,International Association for the Study of Pain(IASP)     

The mutation rates of di-, tri- and tetranucleotide repeats in Drosophila melanogaster

In a recent study, we reported that the combined average mutation rate of 10 di-, 6 tri-, and 8 tetranucleotide repeats in Drosophila melanogaster was 6.3 x 10(-6) mutations per locus per generation, a rate substantially below that of microsatellite repeat units in mammals studied to date (range = 10(-2)-10(-5) per locus per generation). To obtain a more precise estimate of mutation rate for dinucleotide repeat motifs alone, we assayed 39 new dinucleotide repeat microsatellite loci in the mutation accumulation lines from our earlier study. Our estimate of mutation rate for a total of 49 dinucleotide repeats is 9.3 x 10(-6) per locus per generation, only slightly higher than the estimate from our earlier study. We also estimated the relative difference in microsatellite mutation rate among di-, tri-, and tetranucleotide repeats in the genome of D. melanogaster using a method based on population variation, and we found that tri- and tetranucleotide repeats mutate at rates 6.4 and 8.4 times slower than that of dinucleotide repeats, respectively. The slower mutation rates of tri- and tetranucleotide repeats appear to be associated with a relatively short repeat unit length of these repeat motifs in the genome of D. melanogaster. A positive correlation between repeat unit length and allelic variation suggests that mutation rate increases as the repeat unit lengths of microsatellites increase.      

In vitro augmentation of cytotoxicity by N-CWS in peritoneal polymorphonuclear leukocytes (PMNs) induced by PSK,OK-432 or N-CWS

Peritoneal polymorponuclear leukocytes (PMNs) were collected from the peritoneal cavity of C3H/He mice 6 hrs after intraperitoneal (i.p.) injection of 2.5 mg/head of PSK, 1 KE (100 µg)/head of OK-432 or 200 µg/head ofNocardia rubra cell wall skeleton (N-CWS). Withoutin vitro stimulation, these PMNs did not show cytotoxicity to syngeneic MM46 mammary carcinoma cells in⁵¹Cr release assay. Cytotoxicity of these PMNs was augmented by the addition of 25 µg/ml of N-CWS but not of PSK or OK-432 to cultures for the assay at the beginning of the culture. H₂O₂ production of PSK-induced PMNs was increased by thein vitro addition of 25 µg/ml of N-CWS but not of PSK. These results suggest that PSK as well as OK-432 and N-CWS can induce PMNs capable of responding further to N-CWS as the second stimulant.