Reduction of a kinetic model for Na

A 15-state kinetic model for Na^{+} channel gating that describes the coupling between three activation sensors, a two-stage fast inactivation process, and slow inactivated states may be reduced to equations for a 6-state system by application of the method of multiple scales. By expressing the occupation probabilities for closed states and the open state in terms of activation and fast inactivation variables, and assuming that activation has a faster relaxation than inactivation and that the activation sensors are mutually independent, the kinetic equations may be further reduced to rate equations for activation, and coupled fast and slow inactivation that describe spike frequency adaptation, a repetitive bursting oscillation in the neural membrane, and a cardiac action potential with a plateau oscillation. The fast inactivation rate function is, in general, dependent on the activation variable m(t) but may be approximated by a voltage-dependent function, and the rate function for entry into the slow inactivated state is dependent on the fast inactivation variable.

Derivation of Hodgkin-Huxley equations for a Na

The Na^{+} current in nerve and muscle membranes may be described in terms of the activation variable m(t) and the inactivation variable h(t), which are dependent on the transitions of S4 sensors of each of the Na^{+} channel domains DI to DIV. The time-dependence of the Na^{+} current and the rate equations satisfied by m(t) and h(t) may be derived from the solution to a master equation that describes the coupling between two or three activation sensors regulating the Na^{+} channel conductance and a two-stage inactivation process. If the inactivation rate from the closed or open states increases as the S4 sensors activate, a more general form of the Hodgkin-Huxley expression for the open-state probability may be derived where m(t) is dependent on both activation and inactivation processes. The voltage dependence of the rate functions for inactivation and recovery from inactivation are consistent with the empirically determined expressions and exhibit saturation for both depolarized and hyperpolarized clamp potentials.

Knowledge, attitudes, and behavior concerning dental trauma among parents of children attending primary school.

BACKGROUND: Traumatic dental injuries occur frequently in children and adolescents. The purpose of the present study is to examine the levels of knowledge and behaviors regarding dental trauma among parents of children attending primary schools in the Apulia region of Italy. METHODS: The study was carried out using an anonymous questionnaire with closed answers distributed to 2,775 parents who were enrolled based on the entire regional school population. Analyses were conducted using the PROC CORRESP (procedure to perform multiple correspondence analysis) and PROC FASTCLUS (procedure to perform cluster analysis). Statistical significance was set at p-value <0.05. RESULTS: A total 15.5% of the sample reported that their children had experienced dental trauma. Overall, 53.8% of respondents stated that they knew what to do in cases of dental injury. Regarding the time limit within which it is possible to usefully intervene for dental trauma, 56.8% of respondents indicated "within 30 minutes". Of the total sample, 56.5% knew how to preserve a displaced tooth. A total 62.9% of parents felt it was appropriate for their children to use dental guards during sports activities. The multivariate analysis showed that wrong knowledge are distributed among all kinds of subject. Parents with previous experience of dental trauma referred right behaviours, instead weak knowledge and wrong behaviours are associated with parents that easily worried for dental events. CONCLUSIONS: This study showed that most parents reported no experience of dental trauma in their children, and half of them did not know what to do in case of traumatic dental injury and they would intervene within 30 minutes, suggesting that dental trauma may trigger panic. However, they did not have the information needed to best assist the affected child. Motivating parents to assume a preventive approach towards dental trauma may produce positive changes that would result an increase of long-term health benefits among both parents and children.

Voltage dependence of Hodgkin-Huxley rate functions for a multistage K

The activation of a K^{+} channel sensor in two sequential stages during a voltage clamp may be described as the translocation of a Brownian particle in an energy landscape with two large barriers between states. A solution of the Smoluchowski equation for a square-well approximation to the potential function of the S4 voltage sensor satisfies a master equation and has two frequencies that may be determined from the forward and backward rate functions. When the higher-frequency terms have small amplitude, the solution reduces to the relaxation of a rate equation, where the derived two-state rate functions are dependent on the relative magnitude of the forward rates (α and γ) and the backward rates (ß and δ) for each stage. In particular, the voltage dependence of the Hodgkin-Huxley rate functions for a K^{+} channel may be derived by assuming that the rate functions of the first stage are large relative to those of the second stage-α≫γ and ß≫δ. For a Shaker IR K^{+} channel, the first forward and backward transitions are rate limiting (α<γ and δ≪ß), and for an activation process with either two or three stages, the derived two-state rate functions also have a voltage dependence that is of a similar form to that determined for the squid axon. The potential variation generated by the interaction between a two-stage K^{+} ion channel and a noninactivating Na^{+} ion channel is determined by the master equation for K^{+} channel activation and the ionic current equation when the Na^{+} channel activation time is small, and if ß≪δ and α≪γ, the system may exhibit a small amplitude oscillation between spikes, or mixed-mode oscillation, in which the slow closed state modulates the K^{+} ion channel conductance in the membrane.

What do parents know about dental trauma among school-age children? A pilot study.

BACKGROUND: The Ministry of Health published in November 2012 the "National guidelines for the prevention and clinical management of dental trauma in individuals during their developmental age". The aim of this study is to verify the knowledge among parents of children of primary schools to plan corrective actions. METHODS: The study was carried out filling in an anonymous questionnaire distributed to parents enrolled in three primary schools. RESULTS: Despite the publication of the National guidelines, the survey results confirm parents' lack of awareness, knowledge and skills in relation to dental trauma. CONCLUSIONS: This survey will allow to plan a training on interventions aimed at the protection of oral health.

Voltage dependence of a stochastic model of activation of an alpha helical S4 sensor in a K channel membrane.

The voltage dependence of the ionic and gating currents of a K channel is dependent on the activation barriers of a voltage sensor with a potential function which may be derived from the principal electrostatic forces on an S4 segment in an inhomogeneous dielectric medium. By variation of the parameters of a voltage-sensing domain model, consistent with x-ray structures and biophysical data, the lowest frequency of the survival probability of each stationary state derived from a solution of the Smoluchowski equation provides a good fit to the voltage dependence of the slowest time constant of the ionic current in a depolarized membrane, and the gating current exhibits a rising phase that precedes an exponential relaxation. For each depolarizing potential, the calculated time dependence of the survival probabilities of the closed states of an alpha helical S4 sensor are in accord with an empirical model of the ionic and gating currents recorded during the activation process.

Transcriptome analysis reveals coordinated spatiotemporal regulation of hemoglobin and nitrate reductase in response to nitrate in maize roots.

Given the importance of nitrogen for plant growth and the environmental costs of intense fertilization, an understanding of the molecular mechanisms underlying the root adaptation to nitrogen fluctuations is a primary goal for the development of biotechnological tools for sustainable agriculture. This research aimed to identify the molecular factors involved in the response of maize roots to nitrate. cDNA-amplified fragment length polymorphism was exploited for comprehensive transcript profiling of maize (Zea mays) seedling roots grown with varied nitrate availabilities; 336 primer combinations were tested and 661 differentially regulated transcripts were identified. The expression of selected genes was studied in depth through quantitative real-time polymerase chain reaction and in situ hybridization. Over 50% of the genes identified responded to prolonged nitrate starvation and a few were identified as putatively involved in the early nitrate signaling mechanisms. Real-time results and in situ localization analyses demonstrated co-regulated transcriptional patterns in root epidermal cells for genes putatively involved in nitric oxide synthesis/scavenging. Our findings, in addition to strengthening already known mechanisms, revealed the existence of a new complex signaling framework in which brassinosteroids (BRI1), the module MKK2-MAPK6 and the fine regulation of nitric oxide homeostasis via the co-expression of synthetic (nitrate reductase) and scavenging (hemoglobin) components may play key functions in maize responses to nitrate.

Stochastic diffusion model of multistep activation in a voltage-dependent K channel.

The energy barrier to the activated state for the S4 voltage sensor of a K channel is dependent on the electrostatic force between positively charged S4 residues and negatively charged groups on neighboring segments, the potential difference across the membrane, and the dielectric boundary force on the charged residues near the interface between the solvent and the low dielectric region of the membrane gating pore. The variation of the potential function with transverse displacement and rotation of the S4 sensor across the membrane may be derived from a solution of Poisson's equation for the electrostatic potential. By approximating the energy of an S4 sensor along a path between stationary states by a piecewise linear function of the transverse displacement, the dynamics of slow activation, in the millisecond range, may be described by the lowest frequency component of an analytical solution of interacting diffusion equations of Fokker-Planck type for resting and barrier regions. The solution of the Smoluchowski equations for an S4 sensor in an energy landscape with several barriers is in accord with an empirical master equation for multistep activation in a voltage-dependent K channel.

Position-dependent stochastic diffusion model of ion channel gating.

A position-dependent stochastic diffusion model of gating in ion channels is developed by considering the spatial variation of the diffusion coefficient between the closed and open states. It is assumed that a sensor which regulates the opening of the ion channel experiences Brownian motion in a closed region Rc and a transition region Rm, where the dynamics is described by probability densities pc(x,t) and pm(x,t) which satisfy interacting Fokker-Planck equations with diffusion coefficient Dc(x)=Dcexp(gammacx) and Dm(x)=Dmexp(-gammamx). The analytical solution of the coupled equations may be approximated by the lowest frequency relaxation, a short time after the application of a depolarizing voltage clamp, when Dm<

Nonlinear drift-diffusion model of gating in the fast Cl channel.

The dynamics of the open or closed state region of an ion channel may be described by a probability density p(x,t) which satisfies a Fokker-Planck equation. The closed state dwell-time distribution fc(t) derived from the Fokker-Planck equation with a nonlinear diffusion coefficient D(x) proportional to exp(-gamma(x)), gamma>0 and a linear ramp potential Uc(x), is in good agreement with experimental data and it may be shown analytically that if gamma is sufficiently large, fc(t) proportional to t(-2-nu) for intermediate times, where nu=U'c/gamma approximately -0.3 for a fast Cl channel. The solution of a master equation which approximates the Fokker-Planck equation exhibits an oscillation superimposed on the power law trend and can account for an empirical rate-amplitude correlation that applies to several ion channels.

The application of positive matrix factorization in the analysis, characterisation and detection of contaminated soils.

Multivariate factor analytical techniques are widely used for the approximation, in terms of a linear combination of factors, of multivariate experimental data. The chemical composition of soil samples are multivariate in nature and provide datasets suitable for the application of these statistical techniques. Recent developments of multivariate factor analytical techniques have led to the approach of Positive Matrix Factorization (PMF), a weighted least squares fit of a data matrix in which the weights are determined depending on the error estimates of each individual data value. This approach relies on more physically significant assumptions than methods like Principal Components Analysis which is frequently used in the analysis of soil datasets. In this paper we apply PMF to characterise the pollutant source in a set of geographically referenced soil samples taken within a 200 m radius of a site characterised by a high concentration of heavy metals. Each sample has been analysed for major and minor elements (using wavelength-dispersive X-ray fluorescence spectrometry), carbon, hydrogen and nitrogen (using a CHN elemental analyzer) and mercury (using cold-vapour atomic absorption spectrometry). Analysis of the soils using PMF resulted in a successful partitioning of variances into sources related to background soil geochemistry, organic influences and those associated with the contamination. Combining these results with a geostatistical approach successfully demarcated the main source of the combined organic and heavy metal contamination.

Effect of food and gender on the pharmacokinetics of RP 73401, a phosphodiesterase IV inhibitor.

OBJECTIVE: Early exploratory clinical pharmacokinetic studies can provide valuable information for the design and control of subsequent phase 2 studies. This philosophy was instituted for the compound RP 73401, a specific phosphodiesterase IV inhibitor, that was being developed simultaneously for delivery by both oral and pulmonary routes of administration. The objective of these studies was to separately evaluate the effect of food and gender on the pharmacokinetics of RP 73401 using small-scale focused pilot studies. METHODS: In the first study, 400 mcg of inhaled RP 73401 were administered to male and female healthy volunteers (n = 8 f, 8 m. In the second study, 400 mcg oral RP 73401 were administered to healthy male volunteers (n = 8) in the fed and fasted state in a crossover fashion. Serial plasma samples were collected for 24 hours and analyzed for RP 73401 using an HPLC method with post-column photochemical reaction and fluorescence detection that had a minimum quantifiable limit of 10 pg/ml. Pharmacokinetic parameters were calculated using non-compartmental techniques. RESULTS: Comparison of male and female pharmacokinetics following inhalation administration showed no statistically significant differences in the absorption and disposition of RP 73401 with respect to AUC, Cmax, tmax, and t1,2 values. Conversely, RP 73401 administered subsequently to a high fat meal showed a 51% reduction in Cmax and a 5-fold prolongation in tmax as compared to the fasted state. However, there was no statistically significant difference in the systemic availability of RP 73401 as assessed through AUC0-infinity comparisons. CONCLUSIONS: These results successfully allowed the uncomplicated inclusion of females in oral and inhalation studies with RP 73401 and indicated the need to address oral drug dosing conditions in order to minimize sources of pharmacokinetic variability in subsequent phase 2 studies.

Tissue and blood T-lymphocyte subpopulations in erythema nodosum leprosum.

To study T lymphocytes in erythema nodosum leprosum (ENL), monoclonal antibodies were used to identify T-lymphocyte subpopulations in the blood and skin lesions of patients with ENL and patients with nonreactional lepromatous leprosy. The blood of nonreactional lepromatous patients had a lymphopenia and a proportionate reduction in pan T cells, helper-inducer, and suppressor-cytotoxic subsets, but a normal helper-suppressor ratio, as compared with controls. Patients with ENL did not differ significantly from the controls. In skin lesions, an admixture of helper and suppressor phenotypes among foamy histiocytes was found. The ENL tissue had more numerous cells of the helper-inducer phenotype and fewer of the suppressor-cytotoxic phenotype, as compared with nonreaction lepromatous tissues. In 22 patients with simultaneous examination of tissue and blood T-cell subsets, there was no correlation between tissue and blood helper-suppressor ratios, indicating that some sort of selection process brings lymphocytes into tissues from peripheral blood.

Granuloma annulare. Identification of cells in the cutaneous infiltrate by immunoperoxidase techniques.

To characterize the immunopathologic process of granuloma annulare, frozen sections of eight specimens were evaluated with monoclonal antibodies directed against T lymphocytes and the monocyte-macrophage series, in conjunction with immunoperoxidase techniques and with histochemical staining. The predominant lymphocyte was an activated T lymphocyte (Leu 1+, HLA-Dr+) with an excess of helper-inducer phenotype (Leu 3a+), as compared with suppressor-cytotoxic phenotype (Leu 2a+). OKT-6+ Langerhans' cells were observed in the epidermis, and numerous OKT-6+ cells were observed in the perivascular and granulomatous infiltrate. The use of four monoclonal antibodies, having specificity against peripheral blood monocyte antigens, revealed three different staining patterns in the granulomas. Finally, mast cells were present in perivascular and granulomatous infiltrates. Our results demonstrate that the cutaneous infiltrate of granuloma annulare contains all of the principal cell types that characterize cell-mediated immune responses.

[Neonatal hypophosphatasia (author's transl)]. / Ipofosfatasia neonatale.

A case of severe neonatal hypophosphatasia is reported; X-ray aspects are described and differential diagnosis with other forms of foetoneonatal dwarfism is discussed.