Improving outcomes using dental implants: integrating improvements in clinical practice

Modern restorative dentistry is confronted with many challenges related to implant use in the craniofacial region, such as attempting to place implants in esthetically critical sites or anatomically limiting regions of the jaw. To assure a successful implant placement that is satisfactory to both the patient and the dentist, four key areas need to be improved: diagnostic procedures, surgical procedures and outcomes, esthetic results, and prosthetic complications. This article discusses how an integrated approach to these areas can improve clinical practice.     

Surveillance test policy optimization through genetic algorithms using non-periodic intervention frequencies and considering seasonal constraints

In order to maximize systems average availability during a given period of time, it has recently been developed a non-periodic surveillance test optimization methodology based on genetic algorithms (GA). The fact of allowing non-periodic tests turns the solution space much more flexible and schedules can be better adjusted, providing gains in the overall system average availability, when compared to those obtained by an optimized periodic test scheme. This approach, however, turns the optimization problem more complex. Hence, the use of a powerful optimization technique, such as GA, is required.Considering that some particular features of certain systems can turn it advisable to introduce other specific constraints in the optimization problem, this work investigates the application of seasonal constraints for the set of the Emergency Diesel Generation of a typical four-loop pressurized water reactor in order to planning and optimizing its surveillance test policy. In this analysis, the growth of the blackout accident probability during summer, due to electrical power demand increases, was considered. Here, the used model penalizes surveillance test interventions when the blackout probability is higher.Results demonstrate the ability of the method in adapting the surveillance test policy to seasonal constraints. The knowledge acquired by the GA during the searching process has lead to test schedules that drastically minimize test interventions at periods of high blackout probability. It is compensated by more frequent redistributed tests through the periods of low blackout probability in order to improve on the overall average availability at the system level.     

Experimental treatment of brain tumor cells using CD suicide gene

Pro-opiomelanocortin (POMC) is a polyhormone precursor produced predominantly in the pars distalis and pars intermedia of the pituitary gland where it undergoes tissue specific processing to produce a whole array of peptides. We have shown previously that peptides derived from the N-terminal region of POMC are involved in adrenal growth in rats. Using specific two site immunoradiometric assays we have found that the plasma of 17 week old fetal sheep contain a 50 fold excess of pro-gamma-MSH over ACTH. As term approached, the levels of pro-gamma-MSH fell and ACTH rose with evidence of fragmentation of pro-gamma-MSH, suggesting that these peptides act in concert in the development of the fetal adrenal cortex and also provide the necessary drive to bring about parturition. In an attempt to explore the pathophysiology of adrenal function we have cloned human POMC cDNA which led to the discovery of a 9bp addition/deletion mutation in the C-terminus of gamma 3-MSH between positions 67-73. Chinese hamster ovary cells (CHO) cells stably transfected with constructs containing the variant POMC cDNAs have shown a degree of partial processing. Work is currently underway to further investigate the effects of these mutations on the processing by the prohormone converting enzymes PC1 and PC2.     

Multiple pathways are involved in the extracellular processing of MHC class I-restricted peptides

T cell stimulation by certain class I-restricted antigenic peptides, such as the HIV 1 gp160-derived peptide, P18, requires peptide processing by angiotensin-1 converting enzyme (ACE) in FCS. We observed that longer versions of P18 and the murine cytomegalovirus pp89-derived core peptide, pMCMV, which could stimulate T cell hybridomas in FCS, were not as sensitive to the ACE inhibitor captopril as P18. Using cell-free soluble murine class I MHC molecules and protease inhibitors, we found that there are pathways of differing efficiency that use enzymes other than ACE for the proteolytic processing of peptides in serum. The kinetics of the generation of T cell stimulatory activity among P18 variant peptides in serum differed with peptide length, and with the nature of amino and COOH-terminal extensions. Such processing occurs in human plasma as well as in FCS. The understanding of this processing, its kinetics, and its inhibitors can lead to better design of peptide-based therapies, including vaccines.     

Selective increase of alpha2A-adrenoceptor agonist binding sites in brains of depressed suicide victims

The alpha2A- and alpha2C-adrenoceptor subtypes were evaluated in postmortem brains from suicides with depression (n = 22), suicides with other diagnoses (n = 12), and controls (n = 26). Membrane assays with the antagonist [3H]RX821002 (2-[3H]methoxyidazoxan) suggested the presence of alpha2A-adrenoceptors in the frontal cortex and both alpha2C-adrenoceptors and alpha2A-adrenoceptors in the caudate. The proportions in caudate were similar in controls (alpha2A, 86%; alpha2C, 14%), depressed suicides (alpha2A, 91%; alpha2C, 9%), and suicides with other diagnoses (alpha2A, 88%; alpha2C, 12%). Autoradiography of [3H]RX821002 binding under alpha(2B/C)-adrenoceptor-masking conditions confirmed the similar densities of alpha2A-adrenoceptors in the cortex, hippocampus, and striatum from controls and suicides. In the frontal cortex of depressed suicides, competition of [3H]RX821002 binding by (-)-adrenaline revealed a greater proportion (61 +/- 9%) of alpha2A-adrenoceptors in the high-affinity conformation for agonists than in controls (39 +/- 5%). Simultaneous analysis with the agonists [3H]clonidine and [3H]UK14304 and the antagonist [3H]RX821002 in the same depressed suicides confirmed the enhanced alpha2A-adrenoceptor density when evaluated by agonist, but not by antagonist, radioligands. The results indicate that depression is associated with a selective increase in the high-affinity conformation of the brain alpha2A-adrenoceptors.     

Psychosocial experiences influence functioning: new risks, new outcomes

A 34-year-old Japanese woman developed spiking fever, splenomegaly, arthritis, neutrophilia, hyperferritinaemia (22517 ng/ml), elevated C-reactive protein (9.1 mg/ml) and severe thrombocytopenia (1.7 x 10(4)/microl). The patient had depressed antithrombin III activity and abnormally high concentrations of both fibrin degradation products and thrombin-antithrombin complexes. This condition was resistant to high-dose prednisolone therapy (120 mg/day) and non-steroidal anti-inflammatory drugs. We initiated oral methotrexate therapy (7.5 mg/week, orally) with a favourable outcome. The patient's spiking fever subsided on the first day of methotrexate administration. Elevated levels of ferritin and C-reactive protein in the sera rapidly normalised. Methotrexate rapidly improved the disease state which suggested that methotrexate act via modulation of cytokine production or secretion.