Activation of PAF receptor by oxidised LDL in human monocytes stimulates chemokine releases but not urokinase-type plasminogen activator expression

BACKGROUND: We investigated whether the increase of urokinase-type plasminogen activator (uPA) monocyte expression and chemokine releases induced by oxidised low density lipoproteins (LDL), which participate to vascular tissue remodeling and to atherosclerotic plaque rupture, involved proinflammatory phospholipid products having platelet-activating factor (PAF)-like activity via the PAF-receptor pathway. METHODS: uPA monocyte expression was stimulated by either copper ions-oxidised or O2*-/HO* free radical-oxidised LDL. The effects of PAF and oxidised LDL on the production of monocyte chemoattractant protein-1 and interleukin-8 were also examined. RESULTS: Synthetic PAF significantly enhanced chemokine releases (P<0.001) without modifying uPA expression. Copper-oxidised LDL, which exhibit a higher content in lysophosphatidylcholines than free radical-oxidised LDL, induced a significantly higher enhancement in uPA expression (P<0.05). By contrast, free radical-oxidised LDL were more efficient than copper-oxidised LDL to increase chemokine releases (P<0.01). Oxidised LDL-enhanced uPA expressions were not altered by the PAF-receptor antagonist SR27417, whereas increases in chemokine releases induced by oxidised LDL and by PAF were abolished. PAF-acetylhydrolase activity was rapidly and largely inhibited in free radical-oxidised LDL when compared to copper-oxidised LDL, suggesting that free radical-oxidised LDL would contain a higher content in PAF-like products than copper-oxidised LDL. CONCLUSION: Our results indicated that PAF-like oxidation products are responsible for the monocyte chemokine releases, but did not contribute to the enhanced monocyte uPA expression by oxidised LDL.     

Ileocolic intussusception: Predicting the probability of success of ultrasound guided saline enema from clinical and sonographic data

Background/purpose

To identify factors that dim the efficacy of ultrasound guided saline enema (USGSE) and to design a mathematical model for predicting the probability of success of USGSE.

Two mucosal-parenteral schedules to coadminister a multiantigenic formulation against HIV-1 in Balb/c mice

Previous studies showed that simultaneous immunization through the nasal (IN) and subcutaneous (SC) route of a multiantigenic formulation induced a Th1 anti-HIV humoral and cellular immune responses. The formulation was comprised of a recombinant protein of HIV-1 (named CR3; Cellular Response number 3) and the surface and nucleocapsid antigens of hepatitis B virus. This study asks whether four times simultaneous administration through the IN and SC routes (SC+IN) of the multiantigenic formulation induces a similar systemic and mucosal immune responses than two sequential IN priming and two SC boosting (2IN&2SC) inoculations in mice. To answer this question, we tested the same total dose of each antigen per animal in both schedules of inoculation. We found that SC+IN and 2IN&2SC coadministration induced comparable levels of CR3(HIV)-specific IFN-γ-secreting cells and CD8+ cells proliferation in the systemic compartment of animals. Consistent with these findings, a similar Th1 profile considering anti-CR3 IgG1:IGg2a ratio was observed. Additionally, the level of IgG antibodies and the frequency of seroconverting animals in vagina were not different. However, in the case of IgA antibodies the same parameters were significantly higher in the SC+IN group. We also found important level of HBsAg-specific antibodies in serum and vaginal washes.     

ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis

The excision repair cross completing group 1 gene product (ERCC1) and the regulatory subunit of ribonucleotide reductase (RRM1) have been reported as being prognostic of outcome and predictive of therapeutic efficacy in patients with non-small cell lung cancer. Routinely processed surgical specimens from 784 patients from the International Adjuvant Lung Trial were arrayed as tissue microarrays. In situ protein levels were scored with an automated, quantitative analysis system, dichotomized into high and low marker categories, and analyzed for associations with patients' characteristics, survival, and benefit from adjuvant chemotherapy. Scores for both markers were significantly associated with contributing center (P < 0.001) and skewed, with the bulk of scores being low. High scores were more frequent in women for ERCC1 and RRM1 and in older patients and those with adenocarcinoma for RRM1. Low ERCC1 scores indicated significant benefit from adjuvant chemotherapy [hazard ratio (HR) = 0.73 for chemotherapy versus control, P = 0.02]. Although all other survival associations were not statistically significant, low RRM1 scores trended to indicate benefit from adjuvant chemotherapy (HR = 0.84, P = 0.25), and ERCC1 scores were marginally prognostic of survival (HR = 0.77 for high versus low scores, P = 0.10). We conclude that contributing center and specimen quality substantially affect the levels of both markers. Future trials should incorporate the collection and processing of tumor specimens prospectively on standardized protocols to better reveal the impact of biomarkers on clinically relevant outcomes.     

EUS FNA in intraductal papillary mucinous tumors of the pancreas

BACKGROUND/AIMS: There is little information concerning the potential role of fine-needle aspiration guided by endoscopic ultrasonography in the pathologic diagnosis of intraductal papillary mucinous tumors of the pancreas. METHODOLOGY: Patients with an intraductal papillary mucinous tumor of the pancreas suggested by endoscopic ultrasonography underwent fine-needle aspiration guided by endoscopic ultrasonography in order to investigate the presence of mucin and/or cytologic changes consistent with this diagnosis. A group of 111 patients with other pancreatic lesions explored during the same period of time was used as a control group. RESULTS: Fine-needle aspiration guided by endoscopic ultrasonography was safely performed in 19 patients and supported the diagnosis in 17 of them. Nine out of the 17 patients with suspicion of intraductal papillary mucinous tumors of the pancreas went to surgery and this diagnosis was confirmed in the resected specimen in all of them. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS FNA in the diagnosis of IPMT were 82%, 100%, 100%, 92% and 94% respectively. CONCLUSIONS: Fine-needle aspiration guided by endoscopic ultrasonography is a good technique to support the diagnosis of intraductal papillary mucinous tumors of the pancreas and should be considered in this group of patients if pathologic confirmation is judged to be necessary.     

Acanthosis nigricans as the initial paraneoplastic manifestation of gastric adenocarcinoma

We report the case of a 29-year-old man with cutaneous hyperpigmentation located especially in intertriginous areas. The lesions were velvety, rugose and highly pruriginous. The patient was diagnosed with acanthosis nigricans. Initial treatment with topical corticosteroids and oral antihistamines was unsuccessful and, due to suspicion of a paraneoplastic cutaneous syndrome, gastroscopy with sampling for biopsy and abdominal CT were carried out, revealing the existence of an infiltrating gastric adenocarcinoma and underlying adenopathies. The patient underwent total gastrectomy extended to spleen and pancreatic tail and D2 lymph node dissection. Treatment was completed by radiotherapy and chemotherapy to treat lymph node involvement.     

Arterial stiffness predicts severe progression in systemic sclerosis: the ERAMS study

OBJECTIVE: The ERAMS study addressed the value of arterial stiffness in predicting the severity of systemic sclerosis. METHODS: ERAMS was a prospective multicentre cohort study including patients with definite systemic sclerosis. Arterial stiffness was measured by the standardized non-invasive QKd 100-60 method. Clinical evaluation, biological measurements, functional respiratory tests and cardiac Doppler echography were performed at inclusion then each year until 3 years' follow-up was completed. Progression was defined as mild (articulations, muscle, oesophagus or skin involvement) or severe (lung, heart or kidney involvement) by a critical event committee. The prediction of severe progression was studied for QKd 100-60 as well as clinical and biological data at baseline by univariate and multivariate analysis. RESULTS: Ninety-nine patients were included (81 women, 18 men, mean age 57 years, standard deviation 12.5). Although their blood pressure profile was normal, half the patients had increased arterial stiffness (QKd 100-60<200 ms). There was a significant relationship between age-adjusted arterial stiffness and decrease in carbon dioxide diffusion (P<0.03) or haemoglobin rate (P<0.01). By univariate analysis, severe progression after 3 years was predicted by age (P=0.04), lung involvement (P=0.04), diffusion of lung carbon oxide (DLCO) (P<0.01), skin score (P=0.02), haemoglobin (P<0.01) and baseline Qkd 100-60 divided into two classes according to the median (P<0.01). By multivariate analysis, only haemoglobin rate [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.2-0.9] and QKd 100-60 (OR 19.6, 95% CI 1.2-308.2) predicted severe progression of systemic sclerosis. CONCLUSION: The measurement of arterial stiffness by the QKd method is a useful objective method for assessing the prognosis of systemic sclerosis independently from other data.     

Comparison of nine theoretical models for estimating the mechanical power output in cycling

Objective

To assess which of the equations used to estimate mechanical power output for a wide aerobic range of exercise intensities gives the closest value to that measured with the SRM training system.

Methods

Thirty four triathletes and endurance cyclists of both sexes (mean (SD) age 24 (5) years, height 176.3 (6.6) cm, weight 69.4 (7.6) kg and Vo₂max 61.5 (5.9) ml/kg/min) performed three incremental tests, one in the laboratory and two in the velodrome. The mean mechanical power output measured with the SRM training system in the velodrome tests corresponding to each stage of the tests was compared with the values theoretically estimated using the nine most referenced equations in literature (Whitt (Ergonomics 1971;14:419–24); Di Prampero et al (J Appl Physiol 1979;47:201–6); Whitt and Wilson (Bicycling science. Cambridge: MIT Press, 1982); Kyle (Racing with the sun. Philadelphia: Society of Automotive Engineers, 1991:43–50); Menard (First International Congress on Science and Cycling Skills, Malaga, 1992); Olds et al (J Appl Physiol 1995;78:1596–611; J Appl Physiol 1993;75:730–7); Broker (USOC Sport Science and Technology Report 1–24, 1994); Candau et al (Med Sci Sports Exerc 1999;31:1441–7)). This comparison was made using the mean squared error of prediction, the systematic error and the random error.

Results

The equations of Candau et al, Di Prampero et al, Olds et al (J Appl Physiol 1993;75:730–7) and Whitt gave a moderate mean squared error of prediction (12.7%, 21.6%, 13.2% and 16.5%, respectively) and a low random error (0.5%, 0.6%, 0.7% and 0.8%, respectively).

Conclusions

The equations of Candau et al and Di Prampero et al give the best estimate of mechanical power output when compared with measurements obtained with the SRM training system.