Identification of Inflamed Atherosclerotic Lesions In Vivo Using PET-CT

Inflammation plays a major pathogenetic role in the development of atherosclerotic plaques and related thromboembolic events. The identification of vulnerable plaques is of the utmost importance, as this may allow the implementation of more effective preventive and therapeutic interventions. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be useful for tracing inflammation within plaques. However, its relationship to immunohistochemical findings in different territories of the peripheral circulation was not completely elucidated. We aimed to determine whether plaque inflammation could be measured by PET in combination with computer tomography (CT) using FDG and what is the relationship between FDG uptake and immunohistochemical findings in the removed atherosclerotic lesions of the femoral and carotid arteries. The study included 31 patients, 21 patients with high-grade stenosis of the internal carotid artery (ICA) and 10 patients with occlusion of the common femoral artery (CFA), all of whom underwent endarterectomy. Before endarterectomy in all patients, FDG-PET/CT imaging was performed. FDG uptake was measured as the maximum blood—normalized standardized uptake value, known as the target to background ratio (TBR max). TBR max amounted to 1.72?±?0.8, and in patients with ICA, stenosis was not significantly different from patients with CFA occlusion. Immunohistochemical and morphometric analyses of the plaques obtained at endarterectomy showed that the density of T lymphocytes and macrophages (number of cells per square millimeter) was significantly higher in subjects with stenosis of the ICA than in subjects with occlusion of the femoral arteries: lymphocytes, 1.26?±?0.21 vs. 0.77?±?0.29; p?=?0.02 and macrophages, 1.01?±?0.18 vs. 0.69?±?0.23; p?=?0.003. In the whole group of patients, the density of inflammatory cells significantly correlated with FDG uptake represented by PET-TBR max: T lymphocytes, r?=?0.60; p?<?0.01 and macrophages, r?=?0.65; p?<?0.01. The results of our study show that FDG uptake is related to the accumulation of inflammatory cells in atherosclerotic lesions. This finding suggests that FDG uptake reflects the severity of atherosclerotic vessel wall inflammation, and in stenotic lesions, it could be an indicator of their vulnerability. However, data from large outcome studies is needed to estimate the usefulness of this technique in identifying the most dangerous atherosclerotic lesions and vulnerable patients.     

Met-enkephalin modulates lipid peroxidation and total sialic acid level in CBA mice in age- and sex-dependent manners

Age- and sex-associated differences in lipid peroxidation (LPO), and total sialic acid content (TSA) in response to abuse of drugs have been reported both in humans and experimental animals. However, no data on the influence of gender and age on these parameters have been reported for methionine-enkephalin (MENK). In this study we examined the influence of age and gender on MENK-induced LPO levels in the liver and TSA content in splenocytes of CBA mice. LPO production, which was age- and gender-associated was differentially regulated by MENK at a dose of 10 mg or 2.5 mg/kg body weight. At the higher dose, MENK stimulated LPO production in younger males and females but suppressed only in older male mice. At the lower dose, MENK induced strong suppression in males while being without any effect in females. In TSA levels, the age-associated increase was greater in males and much lower in females, with higher TSA levels in younger (2.5, 4.5 months) and decreased levels in older female mice (9 months) being observed. Contrary to the effect on LPO level, TSA level in MENK-treated mice was suppressed in both sexes but only in young 2.5-month-old mice. These data provide evidence that some immunomodulatory properties of MENK are age- and gender-associated which may be relevant to the potential use of MENK as adjuvant therapy in patients with immunocompromised status.     

Outcome of patients with atrial fibrillation after intravenous thrombolysis for cerebral ischaemia

The question of whether i.v. rt-PA is beneficial in patients with ischaemic stroke and atrial fibrillation (AF) remains unresolved. Our objective was to evaluate the outcome of patients with AF who received i.v. rt-PA for stroke in the registries of Lille (France) and Belgrade (Serbia). End-points were poor outcome [modified Rankin Scale (mRS) 3–6], and symptomatic haemorrhagic transformation (sHT) according to ECASS3. Of 734 consecutive patients, 155 (21.2 %) had AF. The unadjusted comparison found patients with AF to be 12 years older, more likely to be women, to have hypertension, and baseline INR > 1.2, and less likely to be smokers. They had higher baseline NIHSS scores, diastolic blood pressure, and serum glucose concentrations, and lower platelet counts. They did not differ for sHT (5.8 vs. 5.5 %; p = 0.893), but they more frequently had poor outcomes (52.3 vs. 35.2 %; p < 0.001) and death (21.9 vs. 9.0 %; p < 0.001). The only independent predictor of sHT was baseline NIHSS (_adjOR 1.05 per 1 point increase; 95 % CI 1.01–1.10). Independent variables associated with poor outcome were age (_adjOR 1.04 for 1 year increase; 95 % CI 1.03–1.06), baseline NIHSS (_adjOR 1.17 per 1 point increase; 95 % CI 1.13–1.21), and sHT (_adjOR 47.6; 95 % CI 10.2–250) but not AF. In patients treated with i.v. rt-PA for cerebral ischaemia, those with AF have worse outcomes because they are older and have more severe strokes at admission. This result suggests that we should focus on prevention and research of more aggressive strategies at the acute stage.     

Incorporation of Copper-Doped Mesoporous Bioactive Glass Nanospheres in Experimental Dental Composites: Chemical and Mechanical Characterization

Experimental dental resin composites incorporating copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) were designed to impart antibacterial and remineralizing properties. The study evaluated the influence of Cu-MBGN on the mechanical properties and photopolymerization of resin composites. Cu-MBGN were synthesized using a microemulsion-assisted sol–gel method. Increasing amounts of Cu-MBGN (0, 1, 5, and 10 wt %) were added to the organic polymer matrix with inert glass micro- and nanofillers while maintaining a constant resin/filler ratio. Six tests were performed: X-ray diffraction, scanning electron microscopy, flexural strength (FS), flexural modulus (FM), Vickers microhardness (MH), and degree of conversion (DC). FS and MH of Cu-MBGN composites with silica fillers showed no deterioration with aging, with statistically similar results at 1 and 28 days. FM was not influenced by the addition of Cu-MBGN but was reduced for all tested materials after 28 days. The specimens with 1 and 5% Cu-MBGN had the highest FS, FM, MH, and DC values at 28 days, while controls with 45S5 bioactive glass had the lowest FM, FS, and MH. DC was high for all materials (83.7–93.0%). Cu-MBGN composites with silica have a potential for clinical implementation due to high DC and good mechanical properties with adequate resistance to aging.     

Anti-CD20 Monoclonal Antibody (Rituximab) for Therapy of Mediastinal CD20-Positive Large B-Cell Non-Hodgkin Lymphoma with a Local Tumor Extension into the Lung of a 10-Year-Old Girl

Intravenous therapy with the anti-CD20 antibody Rituximab has been recently approved for the treatment of CD20 positive non-Hodgkin's lymphoma (NHL) in adults but not in children. The authors present the benefits of its application for mediastinal NHL CD 20+ with a local extension into the lung of a 10-year-old-girl. Receiving the chemotherapy according to study NHL-BFM-95 for high-risk lymphoma the girl did not reach complete remission. Before the last chemotherapy block was started, a computed tomography scan of the thorax showed residue in the right lung. Twenty-five days after the last chemotherapy she received Rituximab at a dose of 375 mg/m 2 by intravenous infusion once a week for a total of four doses without the adverse reactions. Complete remission was achieved. The patient was high risk with lung involvement of lymphoma suggesting a pure prognosis. The results suggest that Rituximab may improve the outcome in high-risk patients and appeared to be safe and effective in children also.     

The influence of smoking and parity on serum markers for Down's syndrome screening.

OBJECTIVE: To evaluate the impact of smoking and number of previous births on maternal serum levels of alpha-fetoprotein and free beta-subunit of human chorionic gonadotropin (free beta-hCG). METHODS: The study included 3,252 completed unaffected singleton pregnancies that proceeded beyond 37 weeks' gestation and resulted with a birth of healthy child. Smoking status of mothers and data concerning gravidity and parity were collected at the sampling date. Serum markers were measured between 13 and 22 gestational weeks, corrected for maternal weight, and converted to multiples of median (MoM) for unaffected pregnancy of the corresponding gestational age. Median MoM values for both markers were examined in relation to both: smoking habits and number of previous births. RESULTS: Smokers had significantly decreased free beta-hCG MoM values compared to nonsmokers (p < 0.001). The median levels showed a negative relationship with the number of previous births. The significance of a decreasing trend was proved, both in smokers (p < 0.001) and nonsmokers (p < 0.001). The median maternal serum alpha-fetoprotein MoM values did not show any significant dependence, neither with regard to smoking (p = 0.65) nor with regard to parity (p = 0.07). CONCLUSIONS: The recommendable adjustment of serum markers to smoking habits, especially concerning the free beta-hCG levels, would be worthwhile. The evidence of the coexisting influence of parity on serum levels of free beta-hCG, both in smokers and nonsmokers, should perhaps be a stimulus for reconsideration of which corrections the screening performance is dependent on.     

Intravenous Ketoprofen in Postoperative Pain Treatment after Major Abdominal Surgery

In recent years considerable attention has been paid to the treatment of postoperative pain, with regard to the favorable effect of adequate analgesia on patient outcome. Multimodal analgesia (e.g., opioids and nonsteroidal anti-inflammatory drugs [NSAIDs] or local anesthetics) is recommended for effective postoperative pain relief. There are few data on the use of NSAIDs in postoperative pain treatment after abdominal surgery. We conducted a randomized, double-blind, placebo-controlled study to assess the analgesic efficacy and safety of ketoprofen after major abdominal surgery. One and nine hours postoperatively patients received 100 mg of ketoprofen i.v. (n = 21) or placebo (n = 22) in addition to a pain-treatment protocol consisting of continuous infusion of tramadol 200 mg and metamizol 5 g over 24 hours with additional 25 mg i.v. tramadol in case of inadequate analgesia. Pain was assessed by numeric rating scale at rest and at deep breath 3, 6, 12, and 24 hours postoperatively and the total dose of tramadol used in the first 24 hours was recorded. Patients in the ketoprofen group had significantly lower pain scores both at rest and at deep breath, at 3 (p < 0.01), 6, and 12 hours (p < 0.05) postoperatively. The 24-hour use of tramadol was significantly lower in the ketoprofen group (p < 0.01), with less nausea and vomiting. There were no bleeding complications or other adverse events related to ketoprofen therapy. The study showed the value of short-term use of ketoprofen to improve the quality of analgesia after major abdominal surgery without significant adverse effects.Presented in part at the 9th Symposium on Intensive Care Medicine, June 24–27, 2002, Brijuni Islands, Croatia, and at the Euroanaesthsia 2004 Meeting, June 5–8, 2004, Lisbon, Portugal     

Alternative models for toxicity testing of xenobiotics

The alternatives to whole-animal testing include endpoint assays, cell and tissue cultures, use of tissue slices, toxicokinetic modelling, and structure-activity relationships and databases. The use of in vitro systems (subcellular fractions, cell lines, primary cell cultures, tissue slices, organ cultures, etc.) as research tools in toxicology is widespread. In the past few years, the apoptosis phenomena were followed by very precise intracellular changes where, through programmed cell death, a cell can be removed from a population. The in vitro systems are ideally suited for investigations of the molecular, cellular and physiological mechanisms of chemically induced toxicity, which cannot readily be studied in vivo for known target organ and target species toxicity studies and for answering specific questions about toxic effects. The main justification for developing in vitro toxicity tests is that they will make toxicology a more scientifically based practice. It is increasingly apparent that the development and incorporation of stepwise testing strategies, combining experimental data from a range of alternative methods (physicochemical techniques, quantitative structure-activity relationships--QSAR, metabolic and kinetic modelling and in vitro tests), provide the most advanced way to predict toxicity, reducing at the same time the number of laboratory animals used for testing.