Nonspecific resistance to bacterial infections. Enhancement by ubiquinone-8

A lipid fraction from Escherichia coli was extracted with apolar solvents and was found to protect mice from a number of experimental bacterial infections. The benzoquinone, ubiquinone-8, was isolated from this extract by high pressure liquid chromatography and identified as such by nuclear magnetic resonance and mass spectrometry. At a dose of 25 mg/kg this substance was found to provide complete protection against otherwise lethal infections with gram-negative and gram-positive bacteria in mice. Treatment was most effective when given intravenously 24 h before infection. In comparative studies, ubiquinone-8 had a clearly higher activity than ubiquinones-4, Q6, and Q10. A highly significant increase in the clearance rate of bacteria from the blood by the spleen and the liver of treated animals, correlated well with the protective effect of ubiquinone-8. The compound stimulated the ability of mouse macrophages to incorporate sheep erythrocytes and significantly increased the number of antibody-producing cells in spleens of mice.     

Synchronous neural interactions assessed by magnetoencephalography: a functional biomarker for brain disorders

We report on a test to assess the dynamic brain function at high temporal resolution using magnetoencephalography (MEG). The essence of the test is the measurement of the dynamic synchronous neural interactions, an essential aspect of the brain function. MEG signals were recorded from 248 axial gradiometers while 142 human subjects fixated a spot of light for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) and their z-transforms (z(ij)(0)) between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of z(ij)(0) successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimer's disease, schizophrenia, Sj?gren's syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results.     

Evidence that Dkk‐1 is dysfunctional in ankylosing spondylitis

Objective

Dkk‐1 is an inhibitory molecule that regulates the Wnt pathway, which controls osteoblastogenesis. This study was undertaken to explore the potential role of Dkk‐1 in ankylosing spondylitis (AS), a prototypical bone‐forming disease.

Methods

Serum Dkk‐1 levels were measured in 45 patients with AS, 45 patients with rheumatoid arthritis (RA), 15 patients with psoriatic arthritis (PsA), and 50 healthy subjects by sandwich enzyme‐linked immunosorbent assay (ELISA). A functional ELISA was used to assess the binding of Dkk‐1 to its receptor (low‐density lipoprotein receptor–related protein 6). Furthermore, we studied the effect of sera from patients with AS and healthy subjects on the activity of the Wnt pathway in the Jurkat T cell model, with and without a neutralizing anti–Dkk‐1 monoclonal antibody, by Western immunoblotting.

Results

Serum Dkk‐1 levels were significantly increased in patients with AS (mean ± SEM 2,730 ± 135.1 pg/ml) as compared with normal subjects (P = 0.040), patients with RA (P = 0.020), and patients with PsA (P = 0.049). Patients with AS receiving anti–tumor necrosis factor α (anti‐TNFα) treatment had significantly higher serum Dkk‐1 levels than patients with AS not receiving such treatment (P = 0.007). Patients with AS studied serially prior to and following anti‐TNFα administration exhibited a significant increase in serum Dkk‐1 levels (P = 0.020), in contrast to patients with RA, who exhibited a dramatic decrease (P < 0.001). Jurkat cells treated with serum from AS patients exhibited increased Wnt signaling compared with cells treated with control serum. In that system, Dkk‐1 blockade significantly enhanced Wnt signaling in control serum–treated, but not AS serum–treated, Jurkat T cells.

Conclusion

Our findings indicate that in patients with AS, circulating bone formation–promoting factors functionally prevail. This can be at least partially attributed to decreased Dkk‐1–mediated inhibition.

     

Antifungal activity of posaconazole and granulocyte colony-stimulating factor in the treatment of disseminated zygomycosis (mucormycosis) in a neutropaenic murine model

The aim of this study was to evaluate the pharmacokinetics and efficacy of posaconazole (PSC) in combination with granulocyte colony-stimulating factor (G-CSF) in a neutropaenic murine model of disseminated zygomycosis (mucormycosis) due to Rhizopus microsporus. Male BALB/c mice were rendered neutropaenic with cyclophosphamide (200 mg kg(-1), intraperitoneally) administered on days -1 and +5 postinfection. Mice were infected with R. microsporus (5 × 10(4) spores ml(-1)) intravenously. Mice were treated with PSC (40 mg kg(-1) day(-1) by gavage) or G-CSF (300 μg kg(-1) day(-1) subcutaneously) or with the combination of PSC and G-CSF. The fungal burden was assessed by culturing the brain, liver, kidneys and lungs. Blood levels of PSC were measured by high performance liquid chromatography. The survival rates were 33%, 27% and 31% for PSC-treated-, G-CSF-treated- and PSC + G-CSF-treated mice, respectively, as compared to 18% for the controls (P = NS). PSC monotherapy and combination therapy significantly reduced the fungal burden in the kidneys, but not in the rest of the organs. Combination therapy was not superior to PSC monotherapy in terms of either survival or reduction in fungal burden. Serum concentrations of PSC were well-above the MIC of PSC for the particular isolate. PSC monotherapy has a modest efficacy against R. microsporus in reducing fungal burden in neutropaenic mice. Combining G-CSF with PSC does not substantially affect the antifungal activity of PSC.     

Recurrent respiratory papillomatosis: a rare chronic disease, difficult to treat, with potential to lung cancer transformation: apropos of two cases and a brief literature review

Recurrent respiratory papillomatosis (RRP), which is caused exclusively by human papilloma virus (HPV), is a rare condition characterized by recurrent growth of benign papillomata in the respiratory tract. The papillomata can occur anywhere in the aerodigestive tract but most frequently in the larynx, affecting both children and adults. The management of this entity remains still challenging since no specific definitive treatment exists. Nevertheless, novel surgical interventions as well as several adjuvant therapies have shown promising results in the long-term palliative management of this debilitating disease. Despite its mostly benign nature, RRP may cause significant morbidity and mortality because of its unpredictable clinical course and especially its tendency, albeit infrequent, for malignant transformation. In this article, we present two patients with RRP; one underwent bronchoscopic laser ablation in combination with inhaled interferon-alpha administration that led to a long-term regression of the disease while the other patient was diagnosed with transformation to squamous cell lung carcinoma with fatal outcome. We include a review of the current literature with special emphasis on RRP management and the potential role of HPV in the development of lung cancer.     

Rare anatomic variation of left gastric artery and right hepatic artery in a female cadaver

The present report describes a rare case in which the left gastric artery arises directly from the abdominal aorta and the right hepatic artery from the superior mesenteric artery, as observed during the dissection of a female cadaver. The left gastric artery usually rises as one of the three branches of the celiac trunk, which was originally described by Haller in 1756, whereas the right hepatic artery usually originates from the proper hepatic artery. The knowledge of the typical anatomy of the abdominal arteries, and their variations, is especially important due to the numerous interventions performed in the abdominal area.     

Arterial stiffness: determinants and relationship to the metabolic syndrome

This study aimed to investigate independent determinants of arterial stiffness and evaluate the association of arterial stiffness with the presence of metabolic syndrome (MS). Demographic characteristics, hemodynamic parameters, and cardiovascular (CV) risk factors were assessed in Greek food industry employees with no history of diabetes or CV disease in order to isolate multiple correlates of arterial stiffness as assessed by pulse wave velocity (PWV). Subsequently, logistic regression analysis was performed using as end point the presence of MS, defined according to the National Cholesterol Education Program. Data from 424 participants (mean age 45.3 -/+ 15.5 years, 298 [70.3%] males, average PWV 8.5 -/+ 3.6 m/s) were analyzed. PWV was higher in men (8.8 -/+ 3.1 m/s) compared to women (7.7 -/+ 2.9 m/s, p < 0.01). Age, systolic blood pressure, and heart rate were isolated as multivariate determinants of PWV (adjusted R2 0.511 [p < 0.0001] in men and 0.538 [p < 0.0001] in women). The overall prevalence of the MS was 14.6%, being similar in both genders. Four variables were shown to be independent predictors of the presence of MS: waist circumference >102 cm (men)/88 cm (women) (OR 8.6, [95% CI 2.8, 20.6], p < 0.001), insulin resistance (homeostasis model assessment >4) (6.3, [2.1, 17.6], p < 0.001), total cholesterol >240 mg/dL (5.5, [1.7, 12.4], p < 0.01), PWV >9 m/s (4.1, [1.5, 9.9], p < 0.01). High PWV, which was found to be mostly determined by advanced age, elevated systolic BP, and accelerated heart rate, appeared to exhibit a strong independent association with the presence of MS together with adiposity and insulin resistance. This index should be considered as a useful marker for CV risk stratification.     

Mefloquine-induced eosinophilic pneumonia

Mefloquine has been widely used for prophylaxis and treatment of patients with chloroquine-resistant malaria; the drug is usually well tolerated. Rarely, adverse effects may be severe, including gastrointestinal disturbances, neuropsychiatric reactions, cardiovascular manifestations, skin lesions, musculoskeletal symptoms, and bone marrow toxicity. We describe a 67-year-old woman with fever, dyspnea on exertion, peripheral blood eosinophilia, and diffuse pulmonary infiltrates on chest radiography. She had taken mefloquine for malaria prophylaxis for an 8-week trip to South Africa. A thorough work-up led to the diagnosis of eosinophilic pneumonia caused by the mefloquine. Her condition improved after the drug was discontinued. To our knowledge, this is the first report of mefloquine-induced eosinophilic pneumonia. Clinicians should be aware of this rare, potential adverse effect of mefloquine.