In vitro studies of poly(methyl methacrylate) adjuvants

Poly(methyl methacrylate) adjuvants, prepared by polymerizing monomeric methyl methacrylate in the presence of influenza virions or by addition of the virions to previously polymerized poly(methyl methacrylate) particles, were studied by means of the hemagglutination test, antibody binding, and electron microscopy. The results indicated that the virions were coated partly when the polymerization was carried out in the presence of the virus, whereas the virions were probably adsorbed when added to polymerized particles.     

Mesencephalic microinjections of neurotensin-(1-13) and its C-terminal fragment, neurotensin-(8-13), potentiate brain stimulation reward

Using the curve shift method, we assessed the effects of ventromedial mesencephalic tegmental (VMT) microinjections of an equimolar concentration of neurotensin-(1-13) (NT-(1-13)) and of its C-terminal fragment, neurotensin-(8-13) (NT-(8-13)), on operant responding for rewarding electrical stimulation of the caudal mesencephalic central gray. The effects of NT-(1-13) and NT-(8-13) on brain stimulation reward (BSR) were also compared to those of systemically administered quinpirole (0.1 and 0.2 mg/kg, s.c.), a direct dopamine agonist, and GBR-12909 (10 and 20 mg/kg, i.p.), a selective dopamine uptake blocker. At the concentration injected, NT-(8-13) was as effective as NT-(1-13) at facilitating BSR, producing significant leftward shifts of the function relating the rate of responding to the stimulation frequency (R/F function); neither form of the peptide was effective when injected in regions dorsal to the VMT. Similarly, GBR-12909 produced a parallel leftward shift of the R/F function, but, unlike NT-(1-13), also significantly increased the asymptotic rates of responding. In contrast, the high dose of quinpirole produced non-parallel leftward shifts of the R/F function and suppressed the asymptote. The similarity between the effects of neurotensin and GBR-12909 on one hand, and the differences between those of neurotensin and quinpirole on the other, suggest that activation VMT neurotensin receptors potentiate BSR by enhancing increases in dopamine neurotransmission that are contingent upon operant responding or rewarding brain stimulation, or both.(ABSTRACT TRUNCATED AT 250 WORDS)     

TEM investigations of biogenic magnetite extracted from the human hippocampus

Modification of chemical and magnetic extraction techniques has yielded biogenic magnetite/maghemite from human hippocampal tissue. Particles were identified using high resolution transmission electron microscopy, electron diffraction and elemental analysis. Though its presence has been inferred from magnetic analyses, this is the first direct observation of magnetic biominerals from the hippocampus.     

The evaluation of lyophilized polymer matrices for administering recombinant human bone morphogenetic protein-2

Novel unitary devices, prepared by lyophilization of viscous solutions of sodium carboxymethylcellulose (CMC) and methylcellulose (MC), were evaluated as sustained-release delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2). In vitro characterization of the unitary devices, which contained rhBMP-2-loaded poly (d,l lactide-co-glycolide) (PLGA) bioerodible particles (BEPs), was conducted over a 2-month period. Determinations included buffer uptake, mass and molecular weight loss and rhBMP-2 release from the unitary devices. CMC devices imbibed approximately 16 times their weight of buffer, while with MC, equilibrium uptake was approximately 6 times the dry weight of the devices. Overall mass loss percentages were approximately 55 and 35%, respectively, for CMC and MC devices. rhBMP-2 release from the devices was essentially a triphasic process: an initial phase during which "free" protein (rhBMP-2 present on the surface and within the pores of the PLGA BEPs) was released, a lag period during which no release was discerned, and then release of "bound" rhBMP-2 (protein adsorbed to the BEPs). The release of bound protein correlated with the mass loss of the polymer which began after 3 weeks. Release from the unitary devices was lower than that from the BEPs alone, due to a retardation effect of the gelled CMC/MC polymers. In rabbits in which full-thickness cranial bone defects were created, the implants were well tolerated and induced significant new bone growth during an 8-week evaluation period. The CMC devices appear to have induced bone earlier (at 2 weeks), but this did not affect eventual 8-week results. CMC devices without rhBMP-2 appeared to provide some bone conduction, in contrast to the blank MC devices.     

Definitive or exploratory periodontal experimentation: an overview of the literature

Definitive and exploratory randomized controlled trials (RCTs) have different goals as well as different design and analysis characteristics. The goal of definitive studies is to provide unequivocal evidence of a treatment's tangible benefit to the patient; a pre-trial-specified hypothesis is tested by use of a pre-trial-specified method. The goal of exploratory studies is to elucidate biological treatment mechanisms, to identify promising treatments, and to generate hypotheses for definitive studies: multiple hypotheses are evaluated to extract as much information from the data as possible. The purposes of this study were: (1) to survey selected design and analysis characteristics of randomized controlled periodontal trials published between 1988 and 1992 (n = 86), and (2) to classify trials as exploratory or definitive studies. The periodontal RCTs surveyed were typical of exploratory studies whose primary goal was to elucidate biological treatment mechanisms. Trial reports indicated the testing of multiple hypotheses (> or = 6 hypothesis tests in 70 of the 86 trials) on a variety of biological markers (86 out of 86 trials). The sample size (< or = 30 subjects in 67 out of 86 trials), duration (< or = 6 months in 65 out of 86 trials), and design and analysis characteristics (e.g., an absence of masking in 57 out of 86 trials) were also typical of exploratory studies which strive to obtain quick answers (short duration) at a low cost (small sample size; accept bias for increased efficiency and a lower cost). No definitive trials were identified. Promising, biologically active, treatments identified in exploratory trials should be evaluated in definitive studies where the primary goal is the procurement of unequivocal evidence of a treatment's tangible benefit to the patient. The costs and benefits of conducting definitive periodontal RCTs to provide such evidence should be investigated.