IL-1 in gingival crevicular fluid following closed root planing and papillary flap debridement

Interleukin (IL)-1 alpha and beta are cytokines which can mediate inflammatory, bone resorbing, and reparative effects in the periodontium, but few longitudinal data exist exploring their role following periodontal therapy. This study examined gingival crevicular fluid (GCF) concentrations of IL-1 alpha and IL-1 beta at sites with shallow sulci (SS) or inflamed moderate/advanced pockets (M/AP) before and 6 months after treatment with closed scaling/root planing (SC/RP) or papillary flap debridement (PFD), all in the same subject (n = 14 patients). No significant differences were noted in IL-1 alpha or beta concentrations (determined with two-site enzyme-linked immunosorbent assays) between SS and M/AP sites at baseline. While both therapies improved clinical parameters of periodontal disease, IL-1 alpha concentration increased significantly (p < 0.05) in M/AP-PFD sites 6 months after treatment, but were unchanged in other groups. IL-1 beta concentrations were numerically lower after therapy, except for a significant increase (p < 0.05) in M/AP-PFD sites. These data suggest that surgical wound healing in an inflamed, plaque-infected site (M/AP-PFD) results in prolonged production of IL-1, which may be a reflection of the extent of tissue trauma and delayed wound healing. In spite of increased IL-1 levels, these sites demonstrated significant short-term improvement in clinical attachment level (+ 1.8 mm, p < or = 0.001) postoperatively.     

Testing an implantable intraspinal drug delivery device in the ewe

OBJECTIVE: The authors report the use of multiple implanted intraspinal port and catheter systems per test animal to study the in vivo functional characteristics and reliability of a new implantable spinal drug delivery port system. METHODS: Four ewes were each implanted with two epidural and one subarachnoid silicone elastomer catheters at the lumbar level. Each catheter was connected in series to one of three Therex filtered spinal delivery ports implanted subcutaneously in a similar grid pattern in each ewe to facilitate percutaneous identification. Saline (2 ml) was injected 3 times weekly in each port. The ease of injection and behavioral responses were recorded for 207-213 days of implantation until sacrifice/necropsy. RESULTS: All ports functioned reliably during the study. However, injection through two of the four subarachnoid catheters resulted in behavioral withdrawal responses intermittently. This behavioral pattern was much less common after epidural port injections. All four subarachnoid and four of eight epidural port and catheter systems were tested with local anesthetic just before sacrifice. Motor block was observed in three of four subarachnoid and three of four epidural port and catheter systems tested. Integrity of the other four epidural ports was tested by injection of methylene blue at sacrifice. This dye did not distribute in the epidural space in one of the latter four epidural ports (not local anesthetic tested) because of a concentric fibrotic reaction about the catheter. Similar fibrotic reactions surrounded the catheters that failed a functional test with local anesthetic. CONCLUSIONS: The implantable intraspinal port system tested functions reliably under repetitive percutaneous access. However, filtering such ports, though desirable to prevent entry of debris into the spinal canal, did not eliminate pericatheter chronic subarachnoid and epidural reaction. The number of test animals required to test 12 ports chronically was reduced by two-thirds without undue trauma to the individual test subject. Chronic percutaneous injection of an implanted subarachnoid system is feasible but may be associated with behavioral effects similar to that seen with chronic epidural systems. Fibrosis around chronic silicone catheters limited functional utility in one-fourth of the implanted test systems. Further study of the potential reactivity of chronic epidural and subarachnoid catheters is indicated.     

Damage to cochlear efferents following AF64A intoxication

Damage to cochlear efferents in chinchillas was assessed using transmission electron microscopy following unilateral treatment with the cholinotoxin ethylcholine mustard aziridinium ion (AF64A). AF64A was diluted in artificial perilymph to concentrations ranging from 0.5 to 100 microM. Survival times ranged from 1 to 12 weeks. At concentrations above 10 microM, widespread damage was noted to efferent fibers within the inner spiral bundle (ISB), tunnel spiral bundle (TSB), tunnel radial fibers (TRF) and efferent terminals at the base of OHCs. This damage included degeneration of fibers and terminals, delamination of mitochondria, vacuolization, and loss of cell membrane. However, at high concentrations, non-specific damage was also noted as thinnings or discontinuities of the membrane of OHCs and afferent fibers. At concentrations between 3 and 10 microM, selective damage was observed to efferent fibers within the ISB, TSB, TRF, and to terminals at the base of the OHCs, with all other structures appearing normal. At concentrations of 0.5 and 1 microM, damage was limited to efferent fibers within the TSB and ISB below the inner hair cells. In general, insult was greatest to middle- and basal-turn efferents, and longer survival times did not produce greater damage to, or loss of, efferents. These data suggest that at low concentrations, AF64A produces a partial yet selective degeneration of cochlear efferents within both the medial and lateral tracts, and that at the lowest concentrations used in these studies, AF64A produces a preferential insult on lateral olivocochlear efferents.     

Arthroplasty implant biomaterial particle associated macrophages differentiate into lacunar bone resorbing cells

OBJECTIVE: To study the pathogenesis of aseptic loosening: in particular, to determine whether macrophages responding to particles of biomaterials commonly used in arthroplasty surgery for arthritis are capable of differentiating into osteoclastic bone resorbing cells, and the cellular and hormonal conditions required for this to occur. METHODS: Biomaterial particles (polymethylmethacrylate, high density polyethylene, titanium, chromium-cobalt, stainless steel) were implanted subcutaneously into mice. Macrophages were isolated from the foreign body granulomas that resulted, cultured on bone slices and coverslips, and assessed for both cytochemical and functional evidence of osteoclast differentiation. RESULTS: Tartrate resistant acid phosphatase (TRAP) negative macrophages isolated from granulomas containing particles of all types of biomaterial composition were capable of differentiating into TRAP positive cells capable of extensive lacunar bone resorption (assessed by scanning electron microscopy). The presence of both UMR106 rat osteoblast-like cells and 1,25-dihydroxy vitamin D3 was necessary for this to occur. CONCLUSION: All implant materials produce wear particles that are the focus of a heavy foreign body macrophage response in the fibrous membrane between a loose implant component and the host bone undergoing resorption. These findings underline the importance of biomaterial wear particle generation and the macrophage response to different types of biomaterial wear particles in the pathogenesis of aseptic loosening.     

Internal excitation of intermediate mass fragments from collisions of 36Ar+Ag nuclei at 35 MeV/nucleon

An extruding wire knife was used to give adult male CFHB rats a minimally traumatic unilateral mechanical lesion of the medial forebrain bundle. In addition, some rats received bilateral intrastriatal injections of one of three fluorescent retrograde tracers either eight days before or eight days after the lesion. Injections made after the lesion revealed that about half of the animals had complete lesions of the nigrostriatal tract, while the other half were incompletely lesioned, the mean proportion of non-axotomized neurons being 23%. Over the 10 weeks following the lesions, the number of tyrosine hydroxylase-immunoreactive cells in the lesioned substantia nigra fell linearly, reaching a mean of 29% of that of the control substantia nigra. In the animals which were completely lesioned, neuronal survival at 10 weeks varied between 6 and 12%. That the disappearance of tyrosine hydroxylase-immunoreactive neurons was due to cell death rather than the loss of tyrosine hydroxylase itself was confirmed by labelling the cells with Fluoro Gold before axotomy; the tracer was seen in survival neurons, microglia and in a few involuted neurons which continued to be tyrosine hydroxylase-immunoreactive. This percentage of neurons surviving axotomy corresponds to the proportion of substantia nigra neurons which project to the contralateral striatum, and these neurons were in the region of the substantia nigra from which the contralateral projection originated. It is concluded that following mechanical transection of the nigrostriatal tract, all truly axotomized substantia nigra neurons die over a period of about 10 weeks.