Mycoplasma pneumoniae Induces Chronic Respiratory Infection, Airway Hyperreactivity, and Pulmonary Inflammation: a Murine Model of Infection-Associated Chronic Reactive Airway Disease

Because chronic Mycoplasma pneumoniae respiratory infection is hypothesized to play a role in asthma, the potential of M. pneumoniae to establish chronic respiratory infection with associated pulmonary disease was investigated in a murine model. BALB/c mice were intranasally inoculated once with M. pneumoniae and examined at 109, 150, 245, 368, and 530 days postinoculation. M. pneumoniae was detected in bronchoalveolar lavage fluid by culture or PCR in 70 and 22% of mice at 109 and 530 days postinoculation, respectively. Lung histopathology was normal up to 368 days postinoculation. At 530 days, however, 78% of the mice inoculated with M. pneumoniae demonstrated abnormal histopathology characterized by peribronchial and perivascular mononuclear infiltrates. A mean histopathologic score (HPS) at 530 days of 5.1 was significantly greater (P < 0.01) than that for controls (HPS score of 0). Serum anti-M. pneumoniae immunoglobulin G was detectable in all of the mice inoculated with M. pneumoniae and was inversely correlated with HPS (r = -0.95, P = 0.01) at 530 days postinoculation. Unrestrained whole-body plethysmography measurement of enhanced pause revealed significantly elevated airway methacholine reactivity in M. pneumoniae-inoculated mice compared with that in controls at 245 days (P = 0.03) and increased airway obstruction at 530 days (P = 0.01). Murine M. pneumoniae respiratory infection can lead to chronic pulmonary disease characterized by airway hyperreactivity, airway obstruction, and histologic inflammation.     

Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury

In order to evaluate in vivo single-photon emission tomography (SPET) method of assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D₁ and D₂ dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O₂. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [¹²⁵I]TISCH and [1251]IBZM for the D₁ and D₂ dopamine receptors, respectively. Using [¹²⁵I]TISCH, we observed no modifications of D₁ receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [¹²⁵I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D₂ dopamine receptor ligand usable for SPET imaging. Therefore, exploration of D₂ receptors by SPET in human neonates suffering from perinatal hypoxia-ischemia may be valuable for the diagnosis and follow-up of cerebral function damages. Correspondence to: D. Guilloteau     

Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Soluble polystyrene derivatives of metal bis(3,4-dicarboxybenzoyl)phthalocyaninates: Synthesis,thermal analysis,and sensitivity towards toxic gases

Polystyrene-bound metal [2,9 or 2,10 (or 2,16 or 2,17) bis(3,4-dicarboxybenzoyl)]phthalocyaninates were synthesized by Friedel-Crafts reaction of polystyrene with the corresponding metal phthalocyaninates. Co(II) and Cu(II) [2,9 or 2,10 (or 2,16 or 2,17) bis(3,4-dicarboxybenzoyl)]-phthalocyaninate (PS-CodaPc and PS-CudaPc) contained 0,13 mmol · g^?1 (12,4 wt.-%) and 0,13 mmol · g^?1 (12,8 wt.-%) of CodaPc and CudaPc, respectively. They were soluble in N,N'-dimethylformamide, but only partially soluble in chloroform, tetrahydrofuran (THF), dimethyl sulfoxide, N-methyl-2-pyrrolidone, and pyridine. The THF extracts contained 0,12 mmol · g^?1 (11,4 wt.-%) and 0,18 mmol ? g^?1 (17,2 wt.-%) of PS-CodaPc and PS-CudaPc, respectively. The thermal stability of the polymers was studied using thermogravimetric and differential thermal analysis in nitrogen and synthetic air atmosphere. The contents of MdaPc(M: metal) in THF-extracted polymers calculated from the data of residue in thermogravimetric analysis are 0,12 mmol · g^?1 for PS-CodaPc and 0,19 mmol · g^?1 for PS-CudaPc. In addition, the sensitive properties of the polymers towards toxic gases were also investigated by quartz microbalance transducers. The results show that the quartz microbalance sensors coated with both polymers were sensitive to NO₂ and chlorinated hydrocarbons, i.e. chloroform and perchloroethylene. The sensitivity to NO₂ was 6,53 · 10^?7 m³ · mL^?1 · s^?1 for PS-CodaPc and 1,90 · 10^?6 m³ · mL^?1 · s^?1 for PS-CudaPc, and that to chloroform and perchloroethylene was 2,33 · 10^?8 and 4,60 · 10^?8 m³ · mL^?1 · s^?1, respectively, for PS-CodaPc and 4,79 · 10^?8 and 9,51 · 10^?7 m³ · mL^?1 · s^?1 for PS-CudaPc.     

Electromechanical properties of perfusion/metabolism mismatch: comparison of nonfluoroscopic electroanatomic mapping with 18F-FDG PET.

The aim of this study was to compare nonfluoroscopic electroanatomic mapping (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of myocardial viability. In particular, we sought to elucidate differences of electromechanical properties between the perfusion/metabolism mismatch as an indicator of a potentially reversible ischemic injury and the perfusion/metabolism match indicating irreversibly damaged myocardial tissue. METHODS: Twenty-one patients with coronary artery disease underwent NOGA mapping of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and resting 201Tl SPECT of myocardial perfusion. RESULTS: Electrical activity was 10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in hypoperfused segments with maintained glucose metabolism (perfusion/metabolism mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused segments with a perfusion/metabolism match and nonviable segments showed significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P < 0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage: r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P < 0.0001). CONCLUSION: In hypoperfused myocardium, electrical activity by NOGA mapping is more closely related to PET metabolic activity than to SPECT myocardial perfusion. As NOGA mapping does not differentiate hypoperfused myocardium with enhanced glucose utilization from normal myocardium, results from NOGA mapping need to be correlated with results from perfusion imaging to identify hypoperfused, yet viable, myocardium and to stratify patients for revascularization procedures.     

Improvement in quality of life after initiation of lamotrigine therapy in patients with epilepsy in a naturalistic treatment setting.

Quality of life is impaired in patients with epilepsy and can be improved by effective therapy. Randomised clinical trials have shown that lamotrigine treatment is associated with improved quality of life. However, little information is available on quality of life or treatment effects in patients with epilepsy in the general population. The objective of this study was to estimate the impact of lamotrigine on quality of life in a naturalistic treatment setting. The study included adult patients with epilepsy in whom lamotrigine therapy was initiated. Each subject completed the Quality of Life in Epilepsy Inventory (QOLIE)-31 quality of life questionnaire at inclusion and at a follow-up visit in the next 4 months. Demographic information and medical history were provided by the investigator. These were evaluated as potential determinants of change in quality of life using logistic regression. Three hundred and forty-one patients were evaluated, 192 starting lamotrigine in combination with another drug, 90 as a first-line monotherapy, 45 as a switch from another drug and 14 as a reduction to monotherapy from a previous combination. Baseline scores on the QOLIE-31 ranged from 53.8 in the combination group to 69.5 in the first-line group. 34.6% of patients were considered to be responders, with no significant differences between treatment regimen. Most improvement was seen for the energy-fatigue and medication effects subscales and, for the first-line group, seizure worry. Seizure type was the only determinant of improvement of quality of life identified. In conclusion, lamotrigine treatment is associated with improved quality of life, regardless of treatment regimen.     

The peri‐microvascular edema in hippocampal CA1 area in a rat model of sepsis

Encephalopathy is a common complication of sepsis. However, little is known about the morphological changes that occur in the brain during sepsis. In this study, fecal peritonitis was induced in Wistar rats, which had been monitored for 4 h before their brains were removed and samples from the CA1 area taken. In addition to higher blood pressure with a decreasing pattern and a significant drop in rectal temperature, an increased heart rate and marked respiratory failure were observed. The tissue was investigated and compared with corresponding hippocampal samples taken from sham‐operated and not operated control groups. Significantly more peri‐microvascular edema was found in the hippocampal CA1 area in the septic group. The percentages of the peri‐microvascular edema were 158.57 ± 3.6%, 122.84 ± 1.5% and 120.24 ± 1.9% in the fecal peritonitis group, sham‐operated and not operated control groups, respectively. The results may suggest that the edema observed around the microvessels may participate in the pathogenesis of the septic encephalopathy probably by causing in the microvascular permeability characteristics.