Mechanical response comparison in an implant overdenture retained by ball attachments on conventional regular and mini dental implants: a finite element analysis

This study investigates the bone/implant mechanical responses in an implant overdenture retained by ball attachments on two conventional regular dental implants (RDI) and four mini dental implants (MDI) using finite element (FE) analysis. Two FE models of overdentures retained by RDIs and MDIs for a mandibular edentulous patient with validation within 6% variation errors were constructed by integrating CT images and CAD system. Bone grafting resulted in 2 mm thickness at the buccal side constructed for the RDIs-supported model to mimic the bone augmentation condition for the atrophic alveolar ridge. Nonlinear hyperelastic material and frictional contact element were used to simulate characteristic of the ball attachment-retained overdentures. The results showed that a denture supported by MDIs presented higher surrounding bone strains than those supported by RDIs under different load conditions. Maximum bone micro strains were up to 6437/2987 and 13323/5856 for MDIs/RDIs under single centric and lateral contacts, respectively. Corresponding values were 4429/2579 and 9557/5774 under multi- centric and lateral contacts, respectively. Bone micro strains increased 2.06 and 1.96-folds under single contact, 2.16 and 2.24-folds under multiple contacts for MDIs and RDIs when lateral to axial loads were compared. The maximum RDIs and MDIs implant stresses in all simulated cases were found by far lower than their yield strength. Overdentures retained using ball attachments on MDIs in poor edentulous bone structure increase the surrounding bone strain over the critical value, thereby damaging the bone when compared to the RDIs. Eliminating the occlusal single contact and oblique load of an implant-retained overdenture reduces the risk for failure.     

Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept‐source optical coherence tomography

Corneal transplantation by full‐thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas. Although corneal transplantation has a high success rate, a shortage of high‐quality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three‐dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept‐source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude‐scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 μm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 μm and 564.5 ± 12.5 μm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 μm confirmed the biocompatibility through the image analysis of the depth‐intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery.      

Mechanisms of adrenergic control of sino-atrial node discharge

Among the mechanisms proposed for the increase in discharge of sino-atrial node (SAN) by norepinephrine (NE) are an increase in the hyperpolarization-activated current I(f) and in the slow inward current I(Ca,L). If I(f) is the primary mechanism, cesium (a blocker of I(f)) should eliminate the positive chronotropic effect of NE. If I(Ca,L), is involved, [Ca(2+)](o) should condition NE effects. We studied the electrophysiological changes induced by NE in isolated guinea pig SAN superfused in vitro with Tyrode solution (both SAN dominant and subsidiary pacemaker mechanisms are present) as well as with high [K(+)](o), higher Cs(+) or Ba(2+) (only the dominant pacemaker mechanism is present). In Tyrode solution, NE (0.5-1microM) increased the SAN rate and adding Cs(+) (approximately 12 mM) caused a decaying voltage tail during diastole in subsidiary pacemakers. NE enhanced the Cs(+)-induced tail, and increased the rate but less than in Tyrode solution. In higher [Cs(+)](o) (15- 18 mM), Ba(2+) (1 mM) or Ba(2+) plus Cs(+) (10 mM) dominant action potentials (not followed by a tail) were present and NE accelerated them as in Tyrode solution. In high [K(+)](o), NE increased the rate in the absence and presence of Cs(+), Ba(2+) or Ba(2+) plus Cs(+). In these solutions, NE increased the overshoot and maximum diastolic potential of dominant action potentials (APs) and increased the rate by steepening diastolic depolarization and shifting the threshold for upstroke to more negative values. High [Ca(2+)](o) alone increased the rate and NE enhanced this action, whereas low [Ca(2+)](o) reduced or abolished the increase in rate by NE. In SAN quiescent in high [K(+)](o) plus indapamide, NE induced spontaneous discharge by decreasing the resting potential and initiating progressively larger voltage oscillations. Thus, NE increases the SAN rate by acting primarily on dominant APs in a manner consistent with an increase of I(Ca,L) and I(K) and under conditions where I(f) is either blocked or not activated. NE INITIATES spontaneous discharge by inducing voltage oscillations unrelated to I(f).     

Simultaneous analysis of prompt and delayed chlorophyll a fluorescence in leaves during the induction period of dark to light adaptation

An attempt is made to reveal the relation between the induction curves of delayed fluorescence (DF) registered at 0.35-5.5 ms and the prompt chlorophyll fluorescence (PF). A simple formulation was proposed to link the ratio of the transient values of delayed and variable fluorescence with the redox state of the primary electron acceptor of Photosystem II--QA, and the thylakoid membrane energization. The term luminescence potential (UL) was introduced, defined as the sum of the redox potential of QA and the transmembrane proton gradient. It was shown that UL is proportional to the ratio of DF to the variable part of PF. The theoretical model was verified and demonstrated by analysing induction courses of PF and millisecond DF, simultaneously registered from leaves of barley--wild-type and the chlorophyll b-less mutant chlorina f2. A definitive correlation between PF and DF was established. If the luminescence changes are strictly due to UL, the courses of DF and PF are reciprocal and the millisecond DF curve resembles the first derivative of the PFt function.     

Climate,body condition and spleen size in birds

Climatic conditions may impact on the body condition of animals and thereby affect their survival prospects. However, climate may also impact directly on the survival prospects of animals by affecting the size of immune defence organs that are used for defence against parasites. We used a large long-term database on body condition and size of the spleen in birds to test for immediate and delayed relationships between climatic conditions as indexed by the North Atlantic Oscillation (NAO) and body condition and spleen mass, respectively. Across 14 species of birds, spleen mass was significantly positively correlated with the NAO index, while the delayed effect of NAO on spleen mass was not significant. Spleen mass was positively related to body condition, but body condition did not depend significantly on NAO or delayed NAO effects. Bird species with a strong positive effect of NAO on spleen mass tended to have small spleens for their body size, while species with a strong negative effect of NAO on spleen mass tended to have relatively large spleens. Since bird species with relatively large spleen have been shown to suffer more from the negative effects of parasites, we can infer that the effects of climate as indexed by NAO on the size of the spleen depends on the importance of parasite-mediated natural selection.Due to an error in the citation line, this revised PDF (published in December 2003) deviates from the printed version, and is the correct and authoritative version of the paper.     

Stem cells from the adult human brain develop into functional neurons in culture

Recent research communications indicate that the adult human brain contains undifferentiated, multipotent precursors or neural stem cells. It is not known, however, whether these cells can develop into fully functional neurons. We cultured cells from the adult human ventricular wall as neurospheres and passed them at the individual cell level to secondary neurospheres. Following dissociation and plating, the cells developed the antigen profile of the three main cell types in the brain (GFAP, astrocytes; O2, oligodendrocytes; and beta-III-tubulin/NeuN, neurons). More importantly, the cells developed the electrophysiological profiles of neurons and glia. Over a period of 3 weeks, neuron-like cells went through the same phases as neurons do during development in vivo, including up-regulation of inward Na+ -currents, drop in input resistance, shortening of the action potential, and hyperpolarization of the cell membrane. The cells developed overshooting action potentials with a mature configuration. Recordings in voltage-clamp mode displayed both the fast inactivating TTX-sensitive sodium current (INa) underlying the rising phase of the action potential and the two potassium currents terminating the action potential in mature neurons (IA and IK, sensitive to 4-AP and TEA, respectively). We have thus demonstrated that the human ventricular wall contains multipotent cells that can differentiate into functionally mature neurons.     

In vitro and in vivo evaluations of biodegradable implants for hormone replacement therapy: Effect of system design and PK-PD relationship

This investigation evaluated the feasibility of using subdermally implantable devices fabricated by nonconventional 3-dimensional printing technology for controlled delivery of ethinyl estradiol (EE₂). In vitro release kinetics of EE₂ and in vivo pharmacokinetics pharmacodynamics in ovariectomized New Zealand White rabbits were carried out to study 3 implant prototypes: implant I (single-channel EE₂ distribution in polycaprolactone polymer core), implant II (homogeneous EE₂ distribution in polycaprolactone polymer matrix), and implant III (concentration-gradient EE₂ distribution in polycaprolactone and poly(dl-lactide-co-glycolide) (50∶50 matrix). EE₂ was found to be released from all the implants in a nonlinear pattern with an order of implant III>implant II>implant I. The noncompartmental pharmacokinetic analysis of plasma EE₂ profiles in rabbits indicated a significant difference (p>.05) in C_max, t_max, and mean residence time between implant I and implants II and III, but no difference in the area under the plasma concentration time curves calculated by trapezoidal rule (AUC) among the implants. For pharmacodynamic studies, endogenous follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were observed to be suppressed following implantation of all implants, which demonstrated that a therapeutically effective dose of EE₂ had been delivered. Furthermore, the noncompartmental analysis of plasma FSH and LH profiles in rabbits showed a significant difference (p<.05) in AUC and the mean residence time between implant III and implants I and II. A good in vivo/in vitro relationship was observed between daily amounts of EE₂ released and plasma profiles of EE₂ for all implants. This relationship suggests that plasma profiles of EE₂ could be predicted from in vitro measurement of daily amount of EE₂ released Therefore, performing in vitro drug release studies may aid in the development of an EE₂ implant with the desired in vivo release rate. Published: September 21, 2001     

The role of glutamate receptors in antipsychotic drug action

Summary. It has recently been postulated that disturbances in glutamatergic neurotransmission may contribute to the pathophysiology of schizophrenia. Therefore the aim of the present study was to evaluate the role of glutamate NMDA and group II metabotropic receptors in the antipsychotic drug action. To this aim the influence of some well-known neuroleptics on cortical NMDA receptors was examined. Furthermore, their behavioral effects were compared with those of the novel agonist of group II glutamate metabotropic receptors, LY 354740, in some animal models of schizophrenic deficits. We found that long-term administration of the typical neuroleptic haloperidol and the atypical one clozapine increased the number of NMDA receptors labelled with [³H]CGP 39653 in different cortical areas. Long-, but not short-term, treatment with haloperidol and raclopride diminished the deficit of prepulse inhibition produced by phencyclidine, which is a model of sensorimotor gating deficit in schizophrenia. In contrast, neither short- nor long-term treatment with clozapine influenced the phencyclidine effect in that model. Acute treatment with LY 354740 reversed neither (1) the deficit of prepulse inhibition produced by phencyclidine or apomorphine, nor (2) the impairment in a delayed alternation task induced by MK-801, which is commonly used to model the frontal lobe deficits associated with schizophrenia. The present study suggests that an increase in the density of cortical NMDA receptors may be important to a longterm neuroleptic therapy. Conversely, the results do not support the role of group II metabotropic glutamate receptors in the antipsychotic drug action. Received August 31, 1999 Accepted September 20, 1999