Dry mouth must not be considered a trivial problem in the population, since it constitutes a phenomenon with many aspects relative to oral function as well as quality of life. Up until today, no global consensus has been reached with regard to the terminology of dry mouth, creating a substantial problem for research, education, diagnosis, and therapy. In this report, salivary gland hypofunction has been selected as the overarching term for subjective symptoms and objective signs of dry mouth. Its different aspects--xerostomia, hyposalivation, and altered saliva composition--are reviewed with respect to prevalence, diagnosis, and etiology. It is concluded that these aspects of salivary gland hypofunction are separate entities, which in many respects are interrelated, constituting not merely a dental but also a medical and social concern.

Practitioners have used hydroxyapatite-coated (HA-coated) endosseous and subperiosteal implants in various forms for many years. These have included root forms in both screw and cylindrical shapes, blades, and subperiosteals. The clinical predictability remains controversial and subject to claims and counterclaims. The early days of dental implantology involving root-form implants recommended their placement in fully edentulous cases only, and anterior to the maxillary sinus and mental foramen. Today's philosophy and rationale of dental implantology include the placement of a single implant replacing a missing natural tooth (especially where the teeth adjacent to the edentulous site have no caries or restorative experience). Implants are used to replace the natural dentition in one quadrant/segment, often preceded or accompanied by ridge augmentation and/or sinus grafting if sufficient bone is not present. So we have to address the clinical predictability of survival in terms of indications, quantity, and quality of bone. Clinical data and experience suggest that hydroxyapatite-coated (HA) dental implants may (and possibly should) be used in (1) Type IV bone, (2) fresh extraction sites, (3) grafted maxillary and/or nasal sinuses, or (4) with short implants (< or = 10 mm in length).

Since dental implants must withstand relatively large forces and moments in function, a better understanding of in vivo bone response to loading would aid implant design. The following topics are essential in this problem. (1) Theoretical models and experimental data are available for understanding implant loading as an aid to case planning. (2) At least for several months after surgery, bone healing in gaps between implant and bone as well as in pre-existing damaged bone will determine interface structure and properties. The ongoing healing creates a complicated environment. (3) Recent studies reveal that an interfacial cement line exists between the implant surface and bone for titanium and hydroxyapatite (HA). Since cement lines in normal bone have been identified as weak interfaces, a cement line at a bone-biomaterial interface may also be a weak point. Indeed, data on interfacial shear and tensile "bond" strengths are consistent with this idea. (4) Excessive interfacial micromotion early after implantation interferes with local bone healing and predisposes to a fibrous tissue interface instead of osseointegration. (5) Large strains can damage bone. For implants that have healed in situ for several months before being loaded, data support the hypothesis that interfacial overload occurs if the strains are excessive in interfacial bone. While bone "adaptation" to loading is a long-standing concept in bone physiology, researchers may sometimes be too willing to accept this paradigm as an exclusive explanation of in vivo tissue responses during experiments, while overlooking confounding variables, alternative (non-mechanical) explanations, and the possibility that different types of bone (e.g., woven bone, Haversian bone, plexiform bone) may have different sensitivities to loading under healing vs. quiescent conditions.

Recently discovered chemically modified tetracyclines have been found to be effective inhibitors of matrix metalloproteinase (MMP)-mediated connective tissue destruction in a variety of pathologic processes, including rheumatoid arthritis and osteoarthritis (OA). Since the histologic techniques used in our laboratory have been validated in Hartley guinea pigs, which have a high incidence of OA-like changes in the proximal tibia, we have used two tetracyclines which have potent inhibitory capacity against various MMPs, doxycycline (Dox) and a compound known as chemically modified tetracyclines (CMT-7). These were given by mouth to a group of guinea pigs for 4 to 8 months, and we assessed the effect of the compound on morphologic and biochemical aspects of OA. We found that prophylactic CMT-7 given orally decreases OA changes in the knee joints both in vitro and in vivo in the guinea pig OA model. Cartilage fibrillation and destruction, in addition to subchondral bone sclerosis and cyst formation, were all decreased in the central compartment of the medial condyle, which is most affected by OA compared with controls. Also collagen, hyaluronan and proteoglycancontent in cartilage was higher in the CMT-7 treated group compared with controls. In contrast, OA changes were not decreased in the Dox group. Our results confirm that various tetracyclines have reduced the severity of OA in animal models, indicating the therapeutic potential of this class of compounds in the future.

The purpose of this paper is two-fold: (1) to review the evidence that osteoporosis and post-menopausal estrogen deficiency are associated with progressive alveolar bone loss and an elevated risk of tooth loss; and (2) to propose the use of tetracyclines, specifically low-dose doxycycline (LDD) (and, perhaps in the future, the chemically modified tetracyclines), to mitigate alveolar bone loss in post-menopausal osteoporotic/osteopenic women. Design concepts for a randomized clinical trial to study the effects of LDD on progressive alveolar bone loss in this patient population are reviewed. Since osteoporosis affects over 20 million people in the United States, progressive alveolar bone loss in this patient group represents a potentially significant public health problem unique from common adult periodontitis. Stopping progressive alveolar bone loss is essential to prevent both tooth loss and micro-architectural deterioration of alveolar bone.

Glycation of proteins, which is accelerated in the diabetic state, has been implicated in many of the long-term complications of diabetes. This process can be inhibited by members of the tetracycline family of compounds. This novel finding is supported by studies conducted on drug (streptozotocin)induced Type I and genetic (ZDF/Gmi-fa/fa) Type II diabetic rats. These animals were orally gavaged daily with 5 mg of doxycycline and a variety of non-antimicrobial chemically modified tetracycline derivatives for time periods of 3 weeks to 11 months, while control untreated diabetic and nondiabetic animals were gavaged with vehicle alone (2% CMC). Blood and tissue samples were collected and analyzed for glucose and glycated proteins. None of the treatments had any effect on the severity of hyperglycemia or the intracellular glycation of hemoglobin of either Type I or II diabetic animals. However, the tetracycline analogues did affect the extracellular glycation of several proteins such as those found in the serum as well as skin collagen. In the Type II (ZDF) animals, initial mortality (3-5 months) was seen only in the doxycycline-treated animals, associated with infection by tetracycline-resistant micro-organisms, which was eventually surpassed by mortality rates in the untreated diabetics (6-9 months). CMT treatment not only decreased mortality but also increased longevity in the Type II diabetic animals, most likely by preventing the development of a number of long-term complications of uncontrolled diabetes, including glycation of proteins, that eventually lead to the demise of untreated diabetic animals.

Collagen gels in vitro can be contracted by fibroblasts. The role of matrix metalloproteinases (MMPs) in the contraction of collagen lattices by human neonatal foreskin fibroblasts (HuFFs) was investigated in tissue culture media supplemented by various doses of known gelatinase inhibitors. Fluorescent assays with model gelatinase substrates and media conditioned by fibroblasts apparently confirmed the ability of chemically modified tetracyclines (CMTs) to act as inhibitors of MMP2, and zymography demonstrated that this was the major cell-derived MMP activity. There were no observable effects on the rate of contraction of attached FPCLs containing 6 x 10(4) HuFFs (passages 18-25) with either CMT-5 or CMT-2 at all concentrations tested (0-100 micrograms/mL). However, at greater than 20 micrograms/mL doxycycline and greater than 5 micrograms/mL CMT-3, FPCL contraction was completely abolished. Quantitative assessment of cell viability by means of the MTT assay in monolayer and qualitatively within the FPCLs with CalceinAM suggested that differences were not due to cytotoxic effects. Seeding FPCLs with lower-passage fibroblasts produced identical trends. These results may implicate the involvement of MMPs in the process of gel contraction, although tetracyclines have effects additional to their ability to inhibit MMPs directly.

The technique of dynamic secondary ion mass spectrometry (SIMS) has, during the 1980s, become a firmly established tool in the microanalytical and microstructural characterization of dental hard tissues. SIMS has proved to be outstandingly suited for charting the distributions of most elements, even at extremely low concentrations, in tooth and bone materials. In-depth concentration profiles as well as surface distribution maps of elements have been recorded with excellent (sub-micron) morphologic resolution. In spite of documented success, only relatively few teams, in a handful of countries, are presently engaged, to any significant extent, in conducting tooth or bone research by the application of SIMS. For dental-medical-surgical laboratories, a partial reason for non-communication is a lack of information about SIMS and its particular assets. Another reason may be connected with an essentially groundless reputation, among non-specialists, of SIMS being an exclusive and expensive technique. Among SIMS laboratories, on the other hand, the inertia in tackling biomineralization is partly due to some particular artifacts of analysis, hitherto not generally known and controlled. The present paper briefly sketches the chief principles of modern SIMS, emphasizing factors of special relevance in the characterization of biomineralized tissues. Examples of recent applications are provided. Present procedures and their limitations are discussed, especially with regard to elemental quantification and imaging. Suggestions for relatively simple modifications to existing routines are offered with the aim of enhancing the ease and availability of SIMS in odontological and surgical research.