The role of PKA and PKC epsilon pathways in prostaglandin E(2)-mediated hypernociception

Background and purpose: Protein kinase (PK) A and the epsilon isoform of PKC (PKC epsilon) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKC epsilon to the development of prostaglandin E(2) (PGE(2))-induced mechanical hypernociception. Experimental approach: Prostaglandin E(2)-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKC epsilon was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws. Key results: Hypernociception induced by PGE(2) (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKC epsilon (PKC epsilon I) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE(2) but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKC epsilon, while the hypernociception induced by paw injection of PKC epsilon agonist was not affected by an inhibitor of PKA (AKAPI). Conclusions and implications: Taken together, these findings are consistent with the suggestion that PKA activates PKC epsilon, which is a novel mechanism of interaction between these kinases during the development of PGE(2)-induced mechanical hypernociception.

Oocyte diameter as a predictor of fertilization and embryo quality in assisted reproduction cycles

Objective: To assess the impact of the mean oocyte diameter (MOD) on occurrence of fertilization and embryo quality in assisted reproduction cycles. Design: Prospective observational study. Setting: Sector of Human Reproduction of the University Hospital, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (HCFMRP-USP). Patient(s): Thirty-five women undergoing intracytoplasmic sperm injection (ICSI) at the University Hospital of Ribeirao Preto from May to October 2007. Intervention(s): MOD assessment. Main Outcome Measure(s): Occurrence of fertilization and qualitative embryo classification on 2nd and 3rd day after ICSI. Result(s): We divided 160 metaphase II oocytes according to MOD into groups A (MOD below the 25th percentile), B (MOD between 25th and 75th percentile), and C (MOD above the 75th percentile). There was no statistically significant association between MOD and the occurrence of fertilization or the qualitative embryo classification on days 2 and 3. There was no statistically significant difference between groups regarding number of cells or the qualitative embryo classification on days 2 and 3. Conclusion(s): The MOD of mature oocytes does not seem to be related to the occurrence of fertilization or to the developmental quality of human embryos on days 2 and 3 after ICSI. (Fertil Steril(R) 2010;93:621-5. (C)2010 by American Society for Reproductive Medicine.)

Masticatory muscle activity in children with a skeletal or dentoalveolar open bite

Forty-five children (31 boys and 14 girls), aged 6-11 years, were included in the study, 15 with a skeletal anterior open bite (SAOB), 15 with a dentoalveolar anterior open bite (DAOB), and 15 with a normal occlusion (CG), defined by clinical evaluation and lateral cephalograms. EMG recordings of the temporal and masseter muscles were performed under maximal voluntary clenching and during chewing. Analysis of variance was used for inter-group analysis, followed by the Tukey post hoc test. A Student`s t-test for paired data was used for intra-group analysis. There were statistically significant differences among the three groups (P < 0.05), with the mean EMG being highest in the CG and lowest in children with a SAOB. The percentage EMG activity during chewing in relation to that during maximal voluntary clenching was more than 100 per cent in the SAOB group. The CG and DAOB groups presented higher EMG activity during clenching compared with chewing (P < 0.001), as well as a greater difference between tasks. In the SAOB group, the neuromuscular system appeared to have a lower capacity to produce EMG activity according to the task, while that in the DAOB group suggests that their functional capacity during growth should also be carefully observed.

Parafoveal letter recognition at reduced contrast in normal aging and in patients with risk factors for AMD

Background Patients with early age-related maculopathy ( ARM) do not necessarily show obvious morphological signs or functional impairment. Many have good visual acuity, yet complain of decreased visual performance. The aim of this study was to investigate the aging effects on performance of parafoveal letter recognition at reduced contrast, and defects caused by early ARM and normal fellow eyes of patients with unilateral age-related macular degeneration (nfAMD). Methods Testing of the central visual field (8 radius) was performed by the Macular Mapping Test (MMT) using recognition of letters in 40 parafoveal target locations at four contrast levels (5, 10, 25 and 100%). Effects of aging were investigated in 64 healthy subjects aged 23 to 76 years (CTRL). In addition, 39 eyes (minimum visual acuity of 0.63; 20/30) from 39 patients with either no visible signs of ARM, while the fellow eye had advanced age-related macular degeneration (nfAMD; n=12), or early signs of ARM (eARM; n=27) were examined. Performance was expressed summarily as a ""field score"" (FS). Results Performance in the MMT begins to decline linearly with age in normal subjects from the age of 50 and 54 years on, at 5% and 10% contrast respectively. The differentiation between patients and CTRLs was enhanced if FS at 5% was analyzed along with FS at 10% contrast. In 8/12 patients from group nfAMD and in 18/27 from group eARM, the FS was statistically significantly lower than in the CTRL group in at least one of the lower contrast levels. Conclusion Using parafoveal test locations, a recognition task and diminished contrast increases the chance of early detection of functional defects due to eARM or nfAMD and can differentiate them from those due to aging alone.

Effect of 4% titanium tetrafluoride solution on dental erosion by a soft drink: An in situ/ex vivo study

Objective: This in situ/ex vivo study assessed the effect of titanium tetrafluoride (TiF4) on permanent human enamel subjected to erosion. Design: Ten volunteers took part in this study performed in two phases. In the first phase (ERO), they wore acrylic palatal appliances containing two enamel blocks, divided into two rows: TiF4 (F) and no-TiF4 (no-F). During the 1st day, the formation of a salivary pellicle was allowed. In the 2nd day, the TiF4 solution was applied on one row (ERO + F), whereas on the other row no treatment was performed (ERO + no-F). From 3rd until 7th day, the blocks were subjected to erosion, 4x per day. In the 2nd phase (no-ERO), the volunteers wore acrylic palatal appliances containing one enamel block, during 2 days, to assess the effect of TiF4 only (no-ERO + F). Enamel alterations were determined using profilometry (wear), microhardness (%SMHC) tests, scanning electron microscope and microprobe analysis. The %SMHC and wear were tested using ANOVA and Tukey`s post hoc tests (p < 0.05). Results: The mean of %SMHC and wear ( mu m) values ( +/- S.D.) were, respectively: ERO + F -73.32 +/- 5.16(A)/2.40 +/- 0.60(a); ERO + no-F -83.49 +/- 4.59B/1.17 +/- 0.48(b) and no-ERO + F -67.92 +/- 6.16(A)/0.21:E 0.09(c). In microscope analysis, the no-F group showed enamel with honeycomb appearance. For F groups, it was observed a surface coating with microcracks. The microprobe analysis revealed the presence of the following elements (%) in groups ERO + F, ERO + no-F and no-ERO + F, respectively: Ca (69.9, 72.5, 66.25); P (25.9, 26.5, 26.06); Ti (3.0, 0, 5.93). Conclusions: The TiF4 was unable to reduce dental erosion. (c) 2007 Elsevier Ltd. All rights reserved.

Analysis of the gutta-percha filled area in C-shaped mandibular molars obturated with a modified MicroSeal technique

To analyse the gutta-percha filled area of C-shaped molar teeth root filled with the modified MicroSeal technique with reference to the radiographic features and the C-shaped canal configuration. Twenty-three mandibular second molar teeth with C-shaped roots were classified according to their radiographic features as: type I - merging, type II - symmetrical and type III - asymmetrical. The canals were root filled using a modified technique of the MicroSeal system. Horizontal sections at intervals of 600 mu m were made 1 mm from the apex to the subpulpal floor level. The percentage of gutta-percha area from the apical, middle and coronal levels of the radiographic types was analysed using the Kruskal-Wallis test. Complementary analysis of the C-shaped canal configurations (C1, C2 and C3) determined from cross-sections from the apical third was performed in a similar way. No significant differences were found between the radiographic types in terms of the percentage of gutta-percha area at any level (P > 0.05): apical third, type I: 77.04%, II: 70.48% and III: 77.13%, middle third, type I: 95.72%, II: 93.17%, III: 91.13% and coronal level, type I: 98.30%, II: 98.25%, III: 97.14%. Overall, the percentage of the filling material was lower in the apical third (P < 0.05). No significant differences were found between the C-shaped canal configurations apically; C1: 72.64%, C2: 79.62%, C3: 73.51% (P > 0.05). The percentage of area filled with gutta-percha was similar in the three radiographic types and canal configuration categories of C-shaped molars. These results show the difficulty of achieving predictable filling of the root canal system when this anatomical variation exists. In general, the apical third was less completely filled.

Strategic maxillary second-molar extraction in Class II malocclusion

Maxillary second-molar extraction in Class II malocclusion is a controversial issue in orthodontics. This treatment protocol is rigorous and not routine. In this case report, we present the orthodontic treatment of a patient with a Class II malocclusion, maxillary crowding, and no mandibular first molars, treated with extraction of the maxillary second molars. The mechanotherapy and indications of maxillary second- molar extraction are discussed. (Am J Orthod Dentofacial Orthop 2009;136:878-86)

Comparative distalization effects of Jones jig and pendulum appliances

Introduction: In this study, we compared the dentoalveolar changes of Class II patients treated with Jones jig and pendulum appliances. Methods: The experimental group comprised 40 Class II malocclusion subjects, divided into 2 groups: group 1 consisted of 20 patients (11 boys, 9 girls) at a mean pretreatment age of 13.17 years, treated with the Jones jig appliance for 0.91 years; group 2 comprised 20 patients (8 boys, 12 grls) at a mean pretreatment age of 13.98 years, treated with the pendulum appliance for 1.18 years. Only active treatment time of molar distalization was evaluated in the predistalization and postdistalization lateral cephalograms. Molar, second premolar, and incisor angular and linear variables were obtained. The intergroup treatment changes in these variables were compared with independent t tests. Results: The maxillary second premolars showed greater mesial tipping and extrusion in the Jones jig group, indicating more anchorage loss during molar distalization with this appliance. The amounts and the monthly rates of molar distalization were similar in both groups. Conclusions: The Jones jig group showed greater mesial tipping and extrusion of the maxillary second premolars. The mean amounts and the monthly rates of first molar distalization were similar in both groups. (Am J Orthod Dentofacial Orthop 2009;135:336-42)

Mental evolution and development: Evidence for secondary representation in children, great apes, and other animals

Recent interest in the development and evolution of theory of mind has provided a wealth of information about representational skills in both children and animals, According to J, Perrier (1991), children begin to entertain secondary representations in the 2nd year of life. This advance manifests in their passing hidden displacement tasks, engaging in pretense and means-ends reasoning, interpreting external representations, displaying mirror self-recognition and empathic behavior, and showing an early understanding of mind and imitation. New data show a cluster of mental accomplishments in great apes that is very similar to that observed in 2-year-old humans. It is suggested that it is most parsimonious to assume that this cognitive profile is of homologous origin and that great apes possess secondary representational capacity. Evidence from animals other than apes is scant. This analysis leads to a number of predictions for future research.

Quantitative analysis of the time courses of enzyme-catalyzed reactions

The catalytic properties of enzymes are usually evaluated by measuring and analyzing reaction rates. However, analyzing the complete time course can be advantageous because it contains additional information about the properties of the enzyme. Moreover, for systems that are not at steady state, the analysis of time courses is the preferred method. One of the major barriers to the wide application of time courses is that it may be computationally more difficult to extract information from these experiments. Here the basic approach to analyzing time courses is described, together with some examples of the essential computer code to implement these analyses. A general method that can be applied to both steady state and non-steady-state systems is recommended. (C) 2001 academic Press.

Molecular Lego (R): non-centrosymmetric alignment within interdigitating layers

(E)-N-Hexadecyl-4-[2-(4-octadecyloxynaphthyl) ethenyl] quinolinium bromide, which has a wide-bodied chromophore and terminal n-alkyl groups, adopts a U-shape when spread at the air-water interface but a stretched conformation when compressed to ca. 35 mN m(-1). The high-pressure phase has a narrow stability range prior to collapse but may be extended from 40 to 60 mN m(-1) by co-spreading the dye in a 1 : 1 ratio with docosanoic acid. The mixed Langmuir-Blodgett (LB) film has a monolayer thickness of 4.6 +/- 0.2 nm which decreases to 2.5 +/- 0.1 nm layer(-1) in the bulk, the reduction arising from an interdigitating layer arrangement, both top and bottom. It is the first example of LB-Lego(R) and, in addition, represents the only fully interdigitating structure with non-centrosymmetrically aligned chromophores. They are tilted 38 degrees from the substrate normal. The second-harmonic intensity increases quadratically with the number of layers, i.e. as I-(N)(2 omega) = (I(1)N2)-N-2 omega, with a second-order susceptibility of chi ((2))(zzz) = 30 pm V-1 at 1064 nm for refractive indices of n(omega) = 1.55 and n(2 omega) = 1.73, d = 2.5 nm layer(-1) and phi = 38 degrees. Angle resolved X-ray photoelectron spectra (XPS) of these films provide no evidence of the bromide counterion, which suggests that it is replaced by OH 2 or HCO3-, which occur naturally in the aqueous subphase, or C21H43COO- from the co-deposited fatty acid. This probably applies to all cationic dyes deposited by the LB technique.

Effect of power Doppler and digital subtraction techniques on the comparison of myocardial contrast echocardiography with SPECT

Objective-To compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients. Design-Cohort study. Setting-Regional cardiothoracic unit. Patients-49 patients (mean (SD) age 61 (11) years; 27 women, 22 men) with known or suspected coronary artery disease were studied with simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole stress. Main outcome measures-Regional myocardial perfusion by SPECT, performed with Tc-99m tetrafosmin, scored qualitatively and also quantitated as per cent maximum activity. Results-Normal perfusion was identified by SPECT in 225 of 270 segments (83%). Contrast echo images were interpretable in 92% of patients. The proportion of normal MCE by grey scale, subtracted, and power Doppler techniques were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts, compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique, specificity was lowest in the lateral wail, although power Doppler was the least affected. Grey scale and subtraction techniques were least accurate in the septal wall, but power Doppler showed particular problems in the apex. On a per patient analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery disease using grey scale, colour coded, and power Doppler, respectively, with a significant difference between power Doppler and grey scale only (p < 0.05). Specificity was also the highest for power Doppler, at 55%, but not significantly different from subtracted colour coded images. Conclusions-Myocardial contrast echo using harmonic power Doppler has greater accuracy than with grey scale imaging and digital subtraction. However, power Doppler appears to be less sensitive for mild perfusion defects.

Quantum criticality

We investigate the theory of quantum fluctuations in non-equilibrium systems having large critical fluctuations. This allows us to treat the limits imposed by nonlinearities to quantum squeezing and noise reduction, and also to envisage future tests of quantum theory in regions of macroscopic quantum fluctuations. A long-term objective of this research is to identify suitable physical systems in which macroscopic 'Schrodinger cat'-like behaviour may be observed. We investigate two systems in particular of much current experimental interest, namely the degenerate parametric oscillator near threshold, and the evaporatively cooled (BEC). We compare the results obtained in the positive-P representation, as a fully quantum mechanical calculation, with the truncated Wigner phase space equation, also known as semi-classical theory. We show when these results agree and differ in calculations taken beyond the linearized approximation. In the region where the largest quantum fluctuations and Schrodinger cat-like behaviour might be expected, we find that the quantum predictions correspond very closely to the semi-classical theory. Nature abhors observing a Schrodinger car.

Determinants of death following burn injury

Background: Burn care has changed considerably. Early surgery, nutritional support, improved resuscitation and novel skin replacement techniques are now well established. The aim of the study was to establish whether changes in management have improved survival following burn injury and to determine the contributory factors leading to non-survival. Methods: This was a retrospective outcome analysis of data collected from a consecutive series of 4094 patients with burns admitted to a tertiary referral, metropolitan teaching hospital between 1972 and 1996, Results: The overall mortality rate was 3.6 per cent. This decreased from 5.3 per cent (1972-1980) to 3.4 per cent (1993-1996) (P = 0.076). The risk of death was increased with increasing burn size (relative risk (RR) 95.90 (95 per cent confidence interval 12.60-729.47) if more than 35 per cent of the total body surface area was burned; P < 0.001) increasing age (RR 7.32 (3.08-17.42) if aged more than 48 years; P < 0.001), inhalation injury (RR 3.61 (2.39-5.47); P < 0.001) and female sex (RR 1.82 (1.23-2.69); P = 0.003). Operative intervention (RR 0.11 (0.06-0.21); P < 0.001) and the presence of an upper limb burn (RR 0.53 (0.35-0.79); P = 0.002) decreased the risk. Conclusion: Modern burn care has decreased the mortality rate. Increasing burn size, increasing age, inhalation injury and female sex increased, while operative intervention and an upper limb burn decreased, the risk of death.

Early Australian experience with infliximab, a chimeric antibody against tumour necrosis factor-alpha, in the treatment of Crohn's disease: is its efficacy augmented by steroid-sparing immunosuppressive therapy?

Background: Tumour necrosis factor-alpha (TNF-alpha) plays an important role in the pathology of Crohn's disease. Infliximab, a chimeric antibody against TNF-alpha, has been shown in controlled clinical trials to be effective in two-thirds of patients with refractory or fistulating Crohn's disease. The factors that determine a clinical response in some patients but not others are unknown. Aims: To document the early Australian experience with infliximab treatment for Crohn's disease and to identify factors that may determine a beneficial clinical response. Methods: Gastroenterologists known to have used infliximab for Crohn's disease according to a compassionate use protocol were asked to complete a spreadsheet that included demographic information, Crohn's disease site, severity, other medical or surgical treatments and a global clinical assessment of Crohn's disease outcome, judged by participating physicians as complete and sustained (remission for the duration of the study), complete but unsustained (remission at 4 weeks but not for the whole study) or partial clinical improvement (sustained or unsustained). Results: Fifty-seven patients were able to be evaluated, with a median follow-up time of 16.4 (4-70) weeks, including 23 patients with fistulae. There were 21 adverse events, including four serious events. Fifty-one patients (89%) had a positive clinical response for a median duration (range) of 11 (2-70) weeks. Thirty patients (52%) had a remission at 4 weeks, 10 of whom had remission for longer than 12 weeks. Forty-two per cent of fistulae closed. Sustained remission (P = 0.065), remission at 4 weeks (P = 0.033) and a positive clinical response of any sort (P = 0.004) were more likely in patients on immunosuppressive therapy, despite there being more smelters in this group. Conclusion: This review of the first Australian experience with infliximab corroborates the reported speed and efficacy of this treatment for Crohn's disease. The excellent response appears enhanced by the concomitant use of conventional steroid-sparing immunosuppressive therapy.