Clinical outcomes following a combined vertical and horizontal alveolar ridge augmentation and two-stage implant placement using either autogenous tooth roots or autogenous bone blocks.

AIM: To assess and compare the short-term clinical outcomes following a combined vertical and horizontal alveolar ridge augmentation and two-stage implant placement using either autogenous tooth roots (TR) or autogenous bone blocks (AB). MATERIALS AND METHODS: A total of n = 27 patients (TR/AB: 13/14) exhibiting n = 31 implants (TR/AB: 14/17) were available for the analysis. Each subject had been allocated to a combined vertical and horizontal alveolar ridge augmentation using either (1) healthy TR (e.g., retained wisdom teeth), or (2) monocortical AB harvested from the retromolar area (i.e. external oblique line). Clinical parameters (e.g., bleeding on probing, BOP; probing pocket depth, PD; mucosal recession, MR) were recorded after a follow-up period of 16.03 ± 4.3 months following implant placement. RESULTS: The survival rates amounted to 100% in both groups. TR and AB grafted sites were associated with similar changes in mean BOP (8.97 ± 27.73%; 11.90 ± 18.97%), PD (0.53 ± 0.49; 0.47 ± 0.67 mm), and MR (0.03 ± 0.13; 0.0 ± 0.02 mm) values. The incidence of peri-implant mucositis and peri-implantitis at the patient level amounted to 15.38% and 0.0% in the TR-, and 28.57% and 7.14% in the AB group. CONCLUSIONS: Both surgical procedures were associated with peri-implant tissue health and stability on the short-term.

Allosteric enhancement of metabotropic glutamate receptor 5 function promotes spatial memory.

Group I metabotropic glutamate receptors (mGluRs) have been implicated in learning and memory formation. Recent findings indicate an important function of the group I mGluR subtype 5. Here, we used the Y-maze spatial alternation task and examined whether enhancement of intrinsic mGluR5 activity immediately after learning, i.e. during a critical period for memory consolidation, would have any consequences on long-term memory retention in rats. Intracerebroventricular application of the allosteric mGluR5 potentiator DFB (3,3'-difluorobenzaldazine) resulted in a marked improvement in spatial alternation retention when it was tested 24 h after training. The promnesic effect increased with the difficulty of the task and was apparently due to a substantial enhancement of consolidation. The applied dose of DFB did not cause behavioral changes in the open field, and was devoid of structural side-effects as evaluated by immunohistochemical examination. Our results suggest an important function of post-training mGluR5 activation in some types of hippocampus-dependent spatial learning.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

Osteointegration of hydroxyapatite-titanium implants coated with nonglycosylated recombinant human bone morphogenetic protein-2 (BMP-2) in aged sheep.

Osteointegration of metal implants into aged organisms can be severely compromised due to reduced healing capacity of bone, lack of precursor cells for new bone formation, or osteoporosis. Here, we report on successful implant healing in a novel model of aged sheep in the presence of nonglycosylated bone morphogenetic protein 2 (BMP-2). Ewes of 8 to 12 years with significant radiologic and histologic signs of osteoporosis and adipocytic bone marrow received a cylindrical hydroxyapatite-titanium implant of 12 x 10 mm. BMP-2 has been produced as a bacterial recombinant fusion protein with maltose-binding protein and in vitro generation of mature BMP-2 by renaturation and proteolytic cleavage. A BMP-2 inhibition ELISA was developed to measure the in vitro release kinetics of bioactive human BMP-2 from immersed solid implant materials by using Escherichia coli expressed and biotinylated recombinant human BMP-2 receptor IA extracellular domain (ALK-3 ECD). The implants were placed laterally below both tibial plateaus, with the left leg implant carrying 380 microg BMP-2. Both implant types became integrated within the following 20 weeks. The control implant only integrated at the cortical bone, and little new bone formation was found within the pre-existing trabecular bone or the marrow cavity. Marrow fat tissue was partially replaced by unspecific connective tissue. In contrast, BMP-2-coated implants initiated significant new bone formation, initially in trabecular arrangements to be replaced by cortical-like bone after 20 weeks. The new bone was oriented towards the cylinder. Highly viable bone marrow appeared and filled the lacunar structures of the new bone. In mechanical tests, the BMP-2-coated implants displayed in average 50% higher stability. This animal model provided first evidence that application of nonglycosylated BMP-2 coated on solid implants may foster bone healing and regeneration even in aged-compromised individuals.

Interleukin-6: a cytokine to forget.

It is known that proinflammatory cytokines such as interleukin-6 (IL-6) are expressed in the central nervous system (CNS) during disease conditions and affect several brain functions including memory and learning. In contrast to these effects observed during pathological conditions, here we describe a physiological function of IL-6 in the "healthy" brain in synaptic plasticity and memory consolidation. During long-term potentiation (LTP) in vitro and in freely moving rats, IL-6 gene expression in the hippocampus was substantially increased. This increase was long lasting, specific to potentiation, and was prevented by inhibition of N-methyl-D-aspartate receptors with (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Blockade of endogenous IL-6 by application of a neutralizing anti-IL-6 antibody 90 min after tetanus caused a remarkable prolongation of LTP. Consistently, blockade of endogenous IL-6, 90 min after hippocampus-dependent spatial alternation learning resulted in a significant improvement of long-term memory. In view of the suggested role of LTP in memory formation, these data implicate IL-6 in the mechanisms controlling the kinetics and amount of information storage.

Effects of methylphenidate on the behavior of male 5xFAD mice.

Alzheimer's disease is a neurodegenerative disorder characterized by a loss of memory and spatial orientation. It is also reported that the dopamine system is affected. Dopamine plays a prominent role in motor functions, motivation, emotion, arousal and reward, and it is important for learning and memory. One model that represents characteristic hallmarks of Alzheimer's disease is the 5xFAD mouse model, in which parenchymal plaque load starts at 2months of age. Transgenic 5xFAD mice show the first behavioral deficits at 6months, which are evident at 9months of age. In this study, we investigated the pharmacological influence of methylphenidate (MPH) on behavioral deficits of 5xFAD mice. Using a battery of behavioral tests, we observed no influence of MPH on anxiety in the elevated plus maze, whereas the locomotion and explorative activity in the open field was increased in transgenic and non-transgenic 5xFAD mice after the application of MPH. Further MPH inhibits habituation in the open field in healthy 5xFAD littermates after the application of 10mg/kg MPH. On the other hand, 10mg/kg MPH improved spatial memory in 6-month-old transgenic 5xFAD males, i.e., at a time point when deficits start to occur. However, in 9-month-old transgenic mice, MPH did not improve persisting learning and memory deficits. We concluded that MPH might improve the non-cognitive, apathy-like behavior (indicated by a reduced exploration), but it has no influence on sustained Alzheimer typical learning and memory deficits.

Spontaneous melanocytosis in transgenic mice.

Clone B is a 2-kb fragment of cloned genomic DNA involved in adipocyte differentiation in vitro. Insertion of this DNA fragment into the genome of a variety of cell lines results in committing the recipient cells to undergo adipocyte differentiation. Construction of transgenic mice with Clone B DNA resulted in an unexpected phenotype--spontaneous melanocytosis. The present study describes the distribution and morphology of melanin-containing lesions in these transgenic mice. Spontaneous melanin-containing dermal lesions appeared on the ears, snout, and perianal regions of transgenic mice by the age of 3-4 months. Multifocal dermal masses rapidly developed into raised lesions, which appeared to spread to adjacent skin. Ultrastructural examination of lymph nodes, spleen, and dermal lesions of these mice revealed membrane-bound melanin with effacement f the organelle structure of severely affected cells. Protein gel electrophoresis revealed elevated activity of tyrosinase in the pinnae, skin, perianal mass, and lymph nodes. This line of transgenic mice may provide a useful model for investigation of the etiology and progression of benign and malignant melanin-containing tumors.

Electrophysiological correlates of handedness and speech perception contrasts.

Auditory evoked responses (AERs) were recorded from left- and right-handed subjects who listened to consonant sounds from different phonetic categories. AERs recorded at parietal scalp regions indicated both groups differentiated categorical differences between speech sounds. However, hand preferences did not affect hemisphere responses to speech sounds.

Block of spatial learning by mGluR agonist tADA in rats.

As demonstrated recently, mGluRs are involved in some forms of learning. We thus investigated the effect of tADA (trans-azetidine-2,4-dicarboxylic acid) applied intracerebroventricularly prior to learning a spatial alternation paradigm. Compared to controls, tADA treated animals were amnesic when tested for retention 24 hr after training. Effects of state-dependency were excluded. These data and our earlier work indicate that both mGluR agonists and antagonists can have memory-disrupting effects.

Syntactic loss versus processing deficit: an assessment of two theories of agrammatism and syntactic comprehension deficits.

This research evaluated Grodzinsky's (1984, 1986a) syntactic loss and Kolk and van Grunsven's (1985) working memory impairment explanations of syntactic comprehension deficits in agrammatic aphasics. Four aphasic patients were evaluated who showed different patterns of impairment on morphological and structural aspects of production. The comprehension tasks compared performance on full and truncated passive sentences. The syntactic loss hypothesis predicted worse performance on truncated than full passives, while the working memory deficit hypothesis predicted the reverse. Neither hypothesis was supported, as the patients performed at a similar level on both types of passives. In addition, there was little relation between the patients' production indices and their comprehension level. The results argue against any global theory of agrammatism that attempts to attribute all agrammatic speech and co-occurring syntactic comprehension deficits to the same source.

Myxoid liposarcoma. An ultrastructural study of two cases.

Two cases in which myxoid liposarcomas were examined by use of light and electron microscopy are presented. The relationship of this tumor to the development of normal adipose tissue is discussed. Most of the ultrastructural features were identical to those of developing white adipose tissue. Features not typical of developing white adipose tissue, such as congeries of 60-Angstrom filaments and large masses of glycogen, are also illustrated and discussed.

Memory retention in old rats: improvement by orotic acid.

The effect of methylglucamine orotate (MGO) on learning and memory was investigated in 24-month-old rats using brightness discrimination in a Y-chamber and active avoidance in a shuttle box. In both learning procedures, an improvement of memory retention following 5-day MGO treatment (225 mg/kg per day) was observed. The retention of untreated old animals was significantly lower compared to 8-week-old rats. MGO treatment resulted in a significant improvement of retention in old rats, which nearly compensated for their memory deficit.

Improvement of shuttle-box avoidance by combinations of orotic acid and central stimulants.

The effect of orotic acid and central stimulants on retention of shuttle-box avoidance was investigated in rats. Orotic acid (100 mg/kg) was injected 30 min before training; caffeine (20mg/kg), strychnine (1 mg/kg), or methylphenidate (10 mg/kg) were injected immediately after training. When given alone, these drugs improved avoidance retention when tested 24 h after training. However, improvement of retention was much more evident when orotic acid was given in combination with a stimulant. The data are discussed in relation to the role of macromolecule synthesis and arousal in memory formation.

Postnatal orotate treatment: effects on learning and memory in adult rats.

During the postnatal period, male Wistar rats were treated with orotate, either from the 6th to 15th, 16th to 25th, or 26th to 35th day of life. Learning and memory were tested in adulthood. Rats that received orotate from the 6th to 15th day showed a better retention of a learned brightness discrimination (Y-maze) than controls. An active avoidance (pole jumping) was learned more quickly by the rats orotate-treated from the 6th to 15th day than by controls. The spontaneous locomotor activity of previously orotate-treated rats was the same as in controls. Body weight measurements revealed no differences between orotate rats and control rats. The results suggest that memory retention in adulthood can be improved by postnatal orotate treatment.

Effect of the memory-improving substance methylglucamine orotate on paradoxical sleep in rats.

The effects of methylglucamine orotate (MGO) were studied on polygraphic sleep recordings in rats for 8 h per day between 8 a.m. and 4 p.m. MGO (225 mg/kg) was injected intraperitoneally immediately prior to the onset of recording. In the acute experiment, the effect of MGO was compared to pre- and post-drug control days. In the chronic experiment, a sequence of 5 control days, 10 days of MGO treatment, and a further 8 control days was tested. Both acute and chronic administration of MGO resulted in increased paradoxical sleep (PS) latency and a small, but significant, decrease in PS during the first 4 h after injection. This effect seems to be specific to PS, as no effects of MGO on waking or total sleep were found. With chronic administration, no PS rebound occurred within the 8-h recording time during the 8-day post-treatment control period. How the RNA precursor can decrease PS and whether this effect may play a role in the memory-improving action of the substance is discussed in terms of an interrelationship between macromolecular synthesis, sleep, and memory, respectively.

Computer-assisted shock-reinforced Y-maze training: a method for studying spatial alternation behaviour.

Y-mazes are widely used for discrimination learning and spatial alternation tasks. We present here a computer-assisted Y-maze model for spatial alternation learning via footshock reinforcement. No intramaze cues are provided and handling between trials is no longer required. Pretraining application of scopolamine (1 mg kg-1) and D-AP5 (2-amino-5-phosphonopentanoate; 0.016 mg) clearly impairs acquisition and retention (tested 24 h after acquisition) of spatial alternation. These effects are not due to state-dependent changes caused by drug treatment. Similar results were reported by others in food-motivated spatial alternation tasks as well as spontaneous alternation paradigms. The data support our model as a useful tool for studying spatial alternation in the Y-maze.

Open field behaviour in rats: role of metabotropic glutamate receptors.

Previous studies have shown that spatial memory retention is affected by the metabotropic glutamate receptor (mGluR) influencing agents (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) and trans-azetidine-2,4-dicarboxylic acid (tADA). In the present investigation we examined whether the mGluR antagonist MCPG (20 mM and 200 mM/5 microliters, respectively) and the agonist tADA (20 mM/5 microliters) have other behavioural effects using the open field test on two successive days. Only minor effects of MCPG (decrease of crossings during the 1st min on day 1) and tADA (increase of rearings on both days) were found. These results suggest that memory influencing doses of MCPG and tADA have no or only little behavioural effects in the open field situation.

Supplemental dietary tyrosine in sepsis and acute hemorrhagic shock.

Previous studies showed that dopamine and norepinephrine levels in rat brain are reduced following stress and that rats fed supplemental tyrosine do not exhibit these reductions. We hypothesized that dietary supplementation with tyrosine would enhance resistance to acute hemorrhagic shock and sepsis by increasing substrate (tyrosine) availability for catecholamine synthesis. Rats were fed either a standard rat chow (6.8 g of tyrosine per kilogram of chow), which supports normal growth, fertility, and longevity, or the same chow supplemented with 10 g of tyrosine per kilogram of chow. Seven days later, the rats underwent cecal ligation and perforation while under intraperitoneal pentobarbital anesthesia. There was a significant increase in survival in the tyrosine-supplemented group. Similarly, in another experiment, tyrosine-supplemented rats were able to tolerate acute fulminant hemorrhagic shock better than were nonsupplemented control animals.

Effects of [des-Tyr-D-Phe3]beta-casomorphin (2-5) on cortical EEG power spectra in rats.

The effects of the peptide [des-Tyr-D-Phe3]beta-casomorphin(2-5) (BCH-325; Pro-D-Phe-Pro-Gly; 2.27, 22.7, and 227 micrograms/kg) on cortical EEG power spectra in rats were studied compared to those of other psychotropic drugs, including diazepam, amitriptyline, haloperidol, and amphetamine. All drugs were injected IP, and cortical EEG power spectra were recorded from freely moving rats for 2 h postinjection. Administration of 22.7 and 227 micrograms/kg BCH-325 resulted in an increase in alpha-2 and beta-1 frequency bands and a decrease in slower frequencies (delta, theta). Our findings show that the effects of BCH-325 on cortical EEG power spectra differ from those of other psychotropic drugs.

Effects of [des-Tyr-D-Phe3]beta-casomorphin (2-5) on sleep pattern in rats.

The effects of the antidepressant-like acting peptide [des-Tyr-D-Phe3]beta-casomorphin(2-5) (Pro-D-Phe-Pro-Gly, BCH-325) on sleep were studied in rats. The rats received subcutaneous injections of BCH-325 in acute experiments (doses: 4, 20, 100, 500 and 2500 nmol/kg) and in a 10-day chronic experiment (50 nmol/kg/day). Acute administration of 20 and 100 nmol/kg enhanced wakefulness, 500 and 2500 nmol/kg enhanced paradoxical sleep, and 4 nmol/kg had no effect. Chronic administration resulted in an increase of paradoxical sleep during the first 5 days of drug treatment. Thus the sleep effects of BCH-325 differ from those of typical antidepressants and other psychotropic drugs.