Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth.

The urokinase-type plasminogen activator (uPA) and uPA receptor (UPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. sc. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR-infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established so U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.     

A randomised double-blind controlled study evaluating the hypothermic effect of 150 microg morphine during spinal anaesthesia for Caesarean section

We studied the hypothermic effect of adding 150 microg morphine during spinal anaesthesia in 60 parturients scheduled for elective caesarean section. All the parturients received intrathecal injection of a solution containing 150 mug morphine or normal saline in addition to 10-12 mg hyperbaric bupivacaine 0.5%. In both groups, a significant decrease in body temperature was noted. There was no difference in the area under the curve for temperature against time for the two groups; however, the maximum decrease in temperature from baseline was significantly larger after morphine than after saline injection (mean (SD) 1.11 (0.61) degrees C vs 0.76 (0.39) degrees C, respectively; p = 0.01) and the time to nadir temperature was significantly longer (59.5 (17.6) min vs 50.4 (15.9) min, respectively; p = 0.047). The lowest temperature observed in the morphine group was 34.3 degrees C. We conclude that intrathecal injection of 150 microg morphine intensified the intra-operative hypothermic effect of bupivacaine spinal anaesthesia for caesarean section.     

Lipopolysaccharide from Prevotella nigrescens stimulates osteoclastogenesis in cocultures of bone marrow mononuclear cells and primary osteoblasts

BACKGROUND AND OBJECTIVE: Lipopolysaccharide is thought to be a major virulence factor of pathogens associated with periodontal diseases and is believed to stimulate bone resorption in vivo. Although Prevotella nigrescens has been implicated in periodontitis, its role in osteoclastogenesis has not been reported. In this study, we investigated the effects of lipopolysaccharide from P. nigrescens on the formation of osteoclasts and the production of cytokines related to osteoclast differentiation. MATERIAL AND METHODS: Mouse bone marrow mononuclear cells were cultured in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL), with or without lipopolysaccharide. Bone marrow mononuclear cells were also cocultured with calvarial osteoblastic cells in the presence or absence of lipopolysaccharide. Osteoclast formation was determined by tartrate-resistant acid phosphatase cytochemistry. The production of osteoprotegerin (OPG), M-CSF, tumor necrosis factor alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and prostaglandin E2 (PGE2) was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: P. nigrescens lipopolysaccharide inhibited osteoclast differentiation from bone marrow mononuclear cells cultured in the presence of M-CSF and RANKL. However, in the coculture system, P. nigrescens lipopolysaccharide stimulated osteoclastogenesis. Notably, P. nigrescens lipopolysaccharide decreased OPG production but increased TGF-beta secretion. In addition, treatment with P. nigrescens lipopolysaccharide increased PGE2 production during the late stage of the culture period. There was no difference in M-CSF and TNF-alpha production. CONCLUSION: These results demonstrate that P. nigrescens lipopolysaccharide stimulates osteoclastogenesis in the coculture system by decreasing the production of OPG and increasing the production of TGF-beta and PGE2. Through the mechanisms involving these factors, P. nigrescens lipopolysaccharide may cause alveolar bone resorption in periodontal diseases.     

G-protein beta3 subunit C825T polymorphism: no association with risk for hypertension and obesity.

OBJECTIVE: Several recent studies have indicated that a C825T polymorphism in the gene encoding the G-protein beta3 subunit is a significant risk factor for hypertension and obesity. In this study, we tested whether this polymorphism is associated with hypertension and obesity in white men. DESIGN: Population-based prospective cohort study. METHODS : We followed a cohort of 903 men, aged 42-61 years at baseline, for an average time of 4.2 years. Genotyping was performed by polymerase chain reaction. RESULTS: The genotype distribution was in Hardy-Weinberg equilibrium: 514 (57%) had the CC genotype, 49 (5%) had the TT genotype and 340 (38%) were heterozygous (T:C = 0.24:0.76). There was no statistically significant difference between the genotype groups in respect to baseline and end of follow-up risk for hypertension or obesity, systolic or diastolic blood pressure, or body mass index. CONCLUSION: We conclude that the C825T polymorphism of the G-protein beta3 subunit gene does not notably contribute to the development of hypertension or obesity, and is not a significant determinant for blood pressure and body mass index in white men.     

Analysis of Taiwanese ichthyosis vulgaris families further demonstrates differences in FLG mutations between European and Asian populations

Background  Mutations in the gene encoding filaggrin ( FLG ) were identified to underlie ichthyosis vulgaris (IV) and also shown to predispose to atopic eczema. Until now, no FLG mutations have been described in the Taiwanese population.
Objectives  To elucidate filaggrin mutations in the Taiwanese population and further to clarify the population genetics of filaggrin gene mutations in the Asian populations.
Methods  In the present study, 12 individuals from four unrelated Taiwanese IV families were examined for FLG mutations. We carried out comprehensive sequencing of the entire FLG coding region using an overlapping polymerase chain reaction strategy.
Results  We identified three FLG mutations in the Taiwanese IV families. One mutation E1795X was a previously unidentified FLG mutation, which might be specific to the Taiwanese. Interestingly, another FLG mutation 3321delA is prevalent in the Japanese population and the other mutation Q2417X was found in the Singaporean Chinese population. No FLG mutation identified in the white European population was found in the Taiwanese population.
Conclusions  The present findings suggest that the Taiwanese population, as an East Asian group, share FLG mutations with both the Japanese and the Singaporean Chinese population. In addition, these results exemplify differences in the population genetics of filaggrin between Europe and Asia.     

An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events

OBJECTIVES: Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases. BACKGROUND: alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human alpha2B-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in diseases associated with enhanced vasoconstriction. METHODS: This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years were followed for an average time of 4.5 years. RESULTS: In this study population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the other two genotypes. The alpha2B-adrenoceptor genotype was not associated with hypertension in this study population. CONCLUSIONS: The D/D genotype of the alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.