A molecular model of MHC class-I-restricted antigen processing.

Cells of higher vertebrates have evolved mechanisms that allow a sample of their intracellular contents to be available for surveillance by the immune system. This display of intracellular material is in the form of peptides bound to cell surface major histocompatibility complex (MHC) class I molecules. In this review, John Monaco presents a model of the mechanisms by which this takes place, based on the recent identification of a number of new genes in the MHC.     

Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis

Nuclear factor kappa B (NF-kappa B) activation has been observed in human atherosclerotic plaques and is enhanced in unstable coronary plaques, but whether such activation has a protective or pathophysiological role remains to be determined. We addressed this question by developing a short-term culture system of cells isolated from human atherosclerotic tissue, allowing efficient gene transfer to directly investigate signaling pathways in human atherosclerosis. We found that NF-kappa B is activated in these cells and that this activity involves p65, p50, and c-Rel but not p52 or RelB. This NF-kappa B activation can be blocked by overexpression of I kappa B alpha or dominant-negative I kappa B kinase (IKK)-2 but not dominant-negative IKK-1 or NF-kappa B-inducing kinase, resulting in selective inhibition of inflammatory cytokines (tumor necrosis factor alpha, IL-6, and IL-8), tissue factor, and matrix metalloproteinases without affecting the antiinflammatory cytokine IL-10 or tissue inhibitor of matrix metalloproteinases. Our results demonstrate that the canonical pathway of NF-kappa B activation that involves p65, p50, c-Rel, and IKK-2 is activated in human atherosclerosis and results in selective up-regulation of major proinflammatory and prothrombotic mediators of the disease.     

Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis

Background: The systemic use of combined amoxicillin and metronidazole (AMX/MET) as an adjunctive treatment to full‐mouth scaling and root planing (FMSRP) has been proposed for the treatment of generalized aggressive periodontitis; however, its effectiveness and clinical safety remain to be defined. The purpose of the present meta‐analysis is to assess the effectiveness of FMSRP + AMX/MET compared to FMSRP alone. Methods: An electronic search of eight databases and a hand‐search of 10 international dental journals were conducted through September 11, 2011. Gain in clinical attachment level (CAL), reduction in probing depth (PD), secondary outcomes, and adverse events were analyzed. A random‐effect model was used to pool the extracted data. The weighted mean difference (MD) with 95% confidence interval (CI) was calculated for continuous outcomes, whereas risk difference (RD) with 95% CI was used for dichotomous data; heterogeneity was assessed with the χ²‐based Cochran Q test and I² statistic. The level of significance was set at P <0.05. Results: After the selection process, six randomized clinical trials were included. Results of the meta‐analysis showed significant CAL gain (MD, 0.42; 95% CI, 0.23 to 0.61; P <0.05) and PD reduction (MD, 0.58; 95% CI, 0.39 to 0.77; P <0.05) in favor of FMSRP + AMX/MET; moreover, no significant RD was found in the occurrence of adverse events (RD, 0.01; 95% CI, ?0.02 to 0.04; P >0.05). Conclusion: The findings of the meta‐analysis seem to support the effectiveness and the clinical safety of FMSRP + AMX/MET; however, future studies are needed to confirm these results.     

Free drug levels monitoring as a detector of false metabolic refractory epilepsy

Unbound and total plasma levels of carbamazepine (CBZ) and phenobarbital (PB) were evaluated in a group of 12 refractory patients out of 397 subjects, with normal values of total drug concentration and unbound levels below the expected ones. We established a minimal acceptable 'subtherapeutic' free drug level, i.e. less than 9.62 micrograms/ml for PB and 1.36 micrograms/ml for CBZ. PB and CBZ dosages were increased during a 3-month period. We observed a normalization of free levels, unaccompanied by a significant decrease in seizure frequency. Free drug level monitoring may prove to be an unchallenged detector of false metabolic refractory epilepsy.     

Effect of oral contraceptives or dexamethasone on plasma beta-endorphin during the menstrual cycle

Several studies have showed a significant increase of plasma beta-endorphin levels during the periovulatory days of the menstrual cycle. The aim of the present study was to investigate the origin of the periovulatory changes of plasma beta-endorphin, trying to discriminate between a possible ovarian and/or pituitary origin. Daily plasma beta-endorphin, luteinizing hormone (LH), and cortisol levels were measured from the 8th to the 20th day of the menstrual cycle in healthy normal-cycling women (10 cases) before and during dexamethasone (DEX; 6 cases) or estroprogestinic treatment with monophasic (5 cases) or triphasic (5 cases) pill. In the control menstrual cycle, during the preovulatory days, a significant increase of plasma beta-endorphin was found. While oral contraceptives abolished the midcycle increase of plasma beta-endorphin, the periovulatory plasma beta-endorphin peak was present during DEX treatment. Plasma cortisol levels did not show any significant change throughout the control menstrual cycle, while they were significantly lowered by the DEX administration and significantly increased during estroprogestinic treatment. These results suggest that the increase of plasma beta-endorphin during the periovulatory days is related to the ovulatory function, and suggest a possible ovarian origin.     

5-En-androstene-3 beta,17 beta-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol.

Adrenal androgens show a dual and apparently opposite effect on the growth of oestrogen-responsive breast cancer: they stimulate growth on their own, but counteract the growth-stimulatory effect of oestrogens. Focusing on the inhibitory action we have studied the effects of 5-en-androstene-3 beta,17 beta-diol (ADIOL) on the growth of oestrogen-responsive MCF-7 breast cancer cells in the presence of oestrogens (oestradiol and diethylstilboestrol), antiestrogens (tamoxifen) and antiandrogens (hydroxyflutamide). The inhibition of oestrogen-stimulated growth, attained with nanomolar concentrations of ADIOL, was not modified by increasing concentrations of diethylstilboestrol up to 100 nM. This inhibition was counteracted by antiandrogens, which were unable to block the ADIOL stimulatory effect in steroid-free medium. On the other hand, in the presence of tamoxifen ADIOL showed an additive antiproliferative activity also in steroid-free medium, rather than the usual stimulatory effect. These results suggest that ADIOL stimulates breast cancer cell growth via oestrogen receptors, but inhibits oestrogen-stimulated growth via androgen receptors.     

Real-time measurement of indoor particulate matter originating from environmental tobacco smoke: a pilot study

Short-term measurement of suspended particulate matter has been recently made possible since the release of laser-operating portable instruments. Data of a pilot study of field evaluation of environmental tobacco smoke (ETS) with a portable instrument are reported. We analysed the concentrations of total suspended particle (TSP) and of the fine particles PM10, PM7, PM2.5 and PM1 released indoor from a single cigarette, and their levels inside smoking- and non-smoking-areas of a restaurant. The results indicate that ETS creates high level indoor particulate pollution, with concentrations of PM10 exceeding air quality standards. This kind of field evaluation could allow a more careful assessing of short-term exposure to ETS and its relevance to public health.